WO1995009159A1 - Quinoxaline derivative as antidiabetic agent - Google Patents

Quinoxaline derivative as antidiabetic agent Download PDF

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Publication number
WO1995009159A1
WO1995009159A1 PCT/JP1994/001559 JP9401559W WO9509159A1 WO 1995009159 A1 WO1995009159 A1 WO 1995009159A1 JP 9401559 W JP9401559 W JP 9401559W WO 9509159 A1 WO9509159 A1 WO 9509159A1
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group
lower alkyl
optionally
alkyl group
formula
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PCT/JP1994/001559
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French (fr)
Inventor
Makoto Komatsu
Hideaki Sato
Shinichi Taira
Masahiro Miyake
Kiyohiko Magata
Hidehiro Yoshida
Atsunori Ueyama
Takao Nishi
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Otsuka Pharmaceutical Company, Limited
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Priority to AU76660/94A priority Critical patent/AU674613B2/en
Priority to EP94927085A priority patent/EP0670831A1/en
Priority to KR1019950702128A priority patent/KR100196356B1/en
Publication of WO1995009159A1 publication Critical patent/WO1995009159A1/en

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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • C07—ORGANIC CHEMISTRY
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    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
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    • C07D241/50—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to ring nitrogen atoms
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    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages

Definitions

  • the present invention relates to an antidiabetic agent.
  • R-CO-NH S0 2 NHCONHR 2 wherein R is a group of the formula:
  • R 2 is alkyl, alkenyl, cycloalkyl, etc. Said compounds are similar to the compounds of this invention in the basic structure and also in the pharmacological activity but are distinguished from the compounds of this invention in the substituent on the phenyl ring in the substituent -CONR 3 R 4 at 2 position of quinoxaline ring.
  • DD-273254-A discloses selective reduction of quinoxaline-di-N - oxide derivatives of the formula:
  • R-- is H, Cl, methyl, or methoxy
  • R 2 is OH, alkoxy or ⁇ - hydroxyethylamino, to give the corresponding N-4-monoxides which are useful as an intermediate for pharmaceuticals and pesticides.
  • R is H, halogen, alkyl, OR 3 , NR 4 R 5 , etc.
  • R 6 and R 7 are H, halogen, alkyl, OR 3 , NR 4 R 5 , etc., which are useful for treating disorders such as asthma, hay-fever, urticaria, eczema or atopic dermatitis.
  • EP-23785 discloses substituted alkoxy-phenoxy-quinoxaline(s), N oxide(s) thereof of the formula:
  • A, B, D, E, J, U and V are H, halogen, nitro, CN, amino, mono- or di - substituted amino, alkyl, alkoxy, carbamoyi, etc.; Y and X are O or S; R 1 and R 2 are H, alkyl, alkenyl, etc.; and W is CN, CSNH , etc., which are useful as pre- and post-emergence selective herbicides.
  • EP-26622 discloses also similar quinoxalinyl-amino-phenoxyalkanoic acids which are useful as pre- and post - emergence selective herbicides.
  • R is H or methyl
  • n is 0 or an integer of 1 to 4
  • 1 and m are 0 or 1 , but no pharmacological activity of these compound is mentioned.
  • DD-284585-A discloses quinoxaline-1 ,4-di-N-oxides of the formula:
  • R 1 is H or optionally substituted alkyl
  • R 2 is H, optionally substituted alkyl, or hydroxyethylcarbamoyl, which are useful as a medicinal feedstuff to protect piglets from gastro-intestinal disorders.
  • BE-721725 discloses 3-carboxamidoquinoxaline-di-N-(1 ,4) - oxides of the formula:
  • is H, alkyl, alkoxy, or Cl;
  • R and R 3 are H, optionally substituted alkyl, or may form with N a 5- or 6- membered heterocyclic ring;
  • X is 0 or S; and
  • R4 is optionally substituted alkyl or optionally substituted phenyl, which have antibacterial activity.
  • Similar compounds are also disclosed in many literatures such as BE-721726, BE-721728, BE-738246, BE-742970, DT-2012743, NL - 7305048, BE-846532, GB-1308370, JP-B-46-23264, JP-B-45-24988, and JP-B • 45-24989.
  • NL-7206031 discloses 2-formyl-3-carbamoyl-quinoxaline 1 ,4 - dioxides of the formula:
  • R-- and R 2 are H, optionally substituted aliphatic or cycloaliphatic group, or form a 5- to 7-membered ring optionally containing 0 or S, Z is NOH or NNHC(Y)R 3 , which have antimicrobial activity.
  • NL-7206601 discloses 2,3-disubstituted quinoxaline-1 ,4-dioxides of the formula:
  • R 1 is phenyl optionally substituted by alkyl, alkoxy, halogen or CF 3
  • R 2 is -CONR 3 R 4 where R 3 and R 4 are H or alkyl or form together alkylene optionally containing O, S or N heteroatom, which are useful as bactericides and amoebicides.
  • R 3 and R 4 are H or alkyl or form together alkylene optionally containing O, S or N heteroatom, which are useful as bactericides and amoebicides.
  • Similar compounds are also disclosed in BE-763377, DT - 2228802, and BE-904482.
  • EP-12725 discloses quinoxaline di-N-oxides of the formula:
  • R 1 is H or alkyl
  • R 2 and R 3 are alkyl or NR 2 R 3 forms 4-5C heterocyclic ring optionally substituted by alkyl
  • R 4 is H, methoxy, methylthio, OH, F, Cl, Br or CN, which are useful as broad-spectrum antimicrobial agents, esp. as veterinary medicaments, and animal growth promoters.
  • CH-619456 discloses 6-phenylthio-quinoxaline-1 ,4-dioxide derivatives of the formula:
  • DT-2052359 discloses quinoxaline 1 ,4-dioxides of the formula:
  • R-* and R 2 are each H, alkyl or alkoxy, or form together methyienedioxy;
  • R 3 is H, optionally unsaturated aliphatic residue (optionally substituted by CN, COOH, carbamoyi, alkylamino, etc.), a 5- or 6-membered cycloaliphatic residue (optionally substituted by alkyl), aryialkyi or furfuryl;
  • R is H, or NR3R4 is optionally unsaturated 5- or 6-membered heterocyclic ring optionally substituted by alkyl;
  • R 5 is optionally substituted and optionally unsaturated aliphatic, cycloaliphatic, araliphatic aromatic or heterocyclic residue, which have antiprotozoal and antibacterial activity. Similar compounds are also disclosed in DT-2052279.
  • DT-2120501 discloses 3-substituted quinoxaline-2-carboxamido - 1 ,4-dioxides of the formula:
  • X is H, methyl, methoxy, CF 3 , F, Cl, or Br
  • Y is alkylthio, alkylsulfinyl, or alkylsulfonyl
  • R' is H or alkyl
  • R" is H or alkyl optionally substituted by amino alkylamino, dialkylamino, pyrrolidino, piperidino, etc., which are useful as broad spectrum antibacterial agents, growth stimulants especially for pigs and poultry.
  • Similar compounds are also disclosed in BE-764088, BE-773396, and DT-2212932.
  • US-3185688 discloses quinoxaline derivatives of the formula:
  • Z is NR(CH 2 ) n NR 1 R 2 , NR(CH 2 ) n Oalkyl, NR(CH 2 ) n Salkyl;
  • X and R are H or alkyl;
  • R-* and R 2 are alkyl, or
  • NR 1 R 2 is morpholino, piperidino, pyrrolidino; and
  • n is 2 - 4, which are useful as tranquilizers.
  • Similar compounds are also disclosed in US-3192212 and FR-2211006.
  • the antidiabetic agent of the present invention comprises as an active ingredient at least one of quinoxaline derivatives of the formula (1): wherein R 1 is hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is hydrogen atom, a lower alkyl group having optionally a halogen substituent, phenyl group, a morpholino-substituted lower alkyl group or an imidazolyl-substituted lower alkyl group, n and m are each 0 or 1 , r is 1 or 2, R 3 and R 4 are the same or different and each a) hydrogen atom; b) a lower alkyl group; c) a phenyl-lower alkoxycarbonyl group; d) a lower alkanoyloxy-substituted lower al
  • R 5 is hydrogen atom, a lower alkoxy-substituted lower alkoxy group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, a halogen atom, nitro group, hydroxy group, a lower alkyl group having optionally a hydroxy substituent, a lower alkenyloxy group, a carboxyl-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a lower alkoxycarbonyl group, a halogen-substituted lower alkoxy group, a hydroxy - substituted lower alkoxy group, a phenyl-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety, a 1 ,3-dioxolanyl group having optionally a substituent selected from a lower alkyl group and a lower al
  • R 8 substitutes on the above heterocyclic group, and is hydrogen atom, oxo group, a lower alkyl group having optionally a hydroxy substituent, a halogen atom, nitro group, a lower alkoxy group, cyano group, a lower alkoxycarbonyl group, a phenyl-lower alkoxy group having optionally an amino group having optionally a lower alkanoyl substituent on the phenyl moiety, a carboxyl - substituted lower alkoxy group, carboxyl group, a lower alkoxycarbonyl - substituted lower alkoxy group, hydroxy group, a lower alkoxy-substituted lower alkoxy group, a lower alkenyloxy group,
  • o -r u ⁇ nsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R 45 bonds to said heterocyclic group and is hydrogen atom, a lower alkyl group, a lower alkoxy-substituted lower alkyl group, phenyl group or oxo group), a group of the formula:
  • R 3 and R 4 may combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, or a salt thereof.
  • the present invention provides also novel quinoxaline derivatives of the formula (1 ) as described above wherein all the symbols are the same as defined above except that n is 0 and the group R 5 excludes hydrogen atom and further provided that when R 1 is hydrogen atom, R 2 is methyl group, R 3 is hydrogen atom, and m is 0, then R 4 is not 2-(imidazol-2-yl)ethyl, 2-(indol-3 - yl)ethyl, or sec-butyl, and a salt thereof.
  • diabetes is caused by the absolute lack of the secretion of insulin and arises either acutely or subacutely, and includes, insulin dependent diabetes mellitus (IDDM) which requires the insulin-treatment, non insulin dependent diabetes mellitus
  • IDDM insulin dependent diabetes mellitus
  • NIDDM insulin-treatment-related diabetes mellitus
  • MRDM malnutrition-related diabetes mellitus
  • a cause of IDDM is estimated to be the destruction of pancreatis ⁇ -cells by auto-immune system.
  • the pancreatis ⁇ - cells are considered to be destroyed by HLA antigen, cytokine virus, etc. (cf.
  • NIDDM Koji NAKANISHI, Tetsuro KOBAYASHI, Mitsuru HARA; Tonyobyogaku (Diabetology) 1989: edited by Mikinori KOSAKA, Yasuo AKANUMA, Shindan- to-Chiryo sha, 1989, pages 226-244).
  • the cause of NIDDM is estimated to be (i) congenital anomaly in pancreatin, i.e. anomaly in adaptability to the increase in insulin consumption, or (ii) disorder in insulin activity induced by various factors such as aging, obesity, stress, etc. (Hiroo IMURA; Tonyobyogaku-no-Shinpo (Progress in Diabetology) 1989, No.
  • the important causes of hyperglycemia is considered to be the decrease in the uptake of glucose at the peripheral tissue, especially at the muscle, and the increase in glucose secretion at the liver.
  • the most common drug therapy for diabetes is treatment with insulin or sulfonylurea agent (agent for promotion of insulin secretion), which are both based on the supplement of insulin, but these treatment have difficulty in strict blood glucose level control, and sometimes they induce hyperinsulin serum or hypoglycemia.
  • a compound which promotes the uptake of glucose at the muscle without promoting the secretion of insulin would be a new kind of hypoglycemic agent without hyperinsulinism nor hypoglycemia and would be useful for treatment of diabetes.
  • the quinoxaline derivatives of the above formula (1 ) and salts thereof (hereinafter referred to as the compounds of the present invention) promote the uptake of 2-deoxyglucose (2DG) against L6 cells, cell line of rat striated muscle (muscular cells) and also promote the consumption of glucose by which they show hypoglycemic activity.
  • the compounds of the present invention show hypoglycemic activity in db/db mice and KK-Ay mice, which are diabetic animal model (L.
  • the compounds of the present invention promote the uptake of glucose at the muscle and do not affect the insulin secretion and the glucose release at the liver so that they do not show acute hypoglycemic activity and do not affect oral glucose tolerance test.
  • the antidiabetic agent of the present invention is useful for treatment of diabetes and diabetic complications such as diabetic blood vessel disorder, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, etc.
  • the lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl, etc.
  • the halogen atom is fluorine atom, chlorine atom, bromine atom or iodine atom.
  • the lower alkyl group having optionally a halogen substituent includes, for example, in addition to the above mentioned lower alkyl groups, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms having optionally 1 to 3 halogen substituents, such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromo - methyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl,
  • the morpholino-substituted lower alkyl group includes a morpholino-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, morpholinomethyl, 2-morpholinoethyl, 1-morpholinoethyl, 3-(2-morpholinyl) - propyl, 4-(3-morpholinyl)butyl, 1 ,1-dimethyl-2-(2-morpholinyl)ethyl, 5- morpholinopentyl, 6-morpholinohexyl, 2-methyl-3-morpholinopropyl, etc.
  • the imidazolyl-substituted lower alkyl group includes an imidazolyl-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (1 - imidazolyl)methyl, 2-(1-imidazolyl)ethyl, 1-(2-imidazolyl)ethyl, 3-(4-imidazolyl) - propyl, 4-(5-imidazolyl)butyl, 1 ,1-dimethyl-2-(2-imidazolyl)ethyl, 5-(4 - imidazoly pentyl, 6-(1-imidazolyl)hexyl, 2-methyl-3-(1-imidazolyl)propyl, etc.
  • the lower alkylene group includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1 - methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene, etc.
  • the lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.
  • the amino group being optionally substituted by a lower alkyl group includes an amino group which may optionally be substituted by 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N - butylamino, N-methyl-N-hexylamino, and the like.
  • the lower alkyl group having optionally a hydroxy substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 1-hydroxyisopropyl, 3-hydroxy - propyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1 ,1-dimethyl-2-hydroxyethyl, 5,5,4 - trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 2-methyl-3-hydroxypropyl, 2,3-dihydroxyethyl, 3,4-dihydroxybutyl, 5,6-dihydroxyhexyl, and the like.
  • the lower alkenyloxy group includes a straight chain or branched chain alkenyloxy group having 2 to 6 carbon atoms, for example, allyloxy, 2 - butenyloxy, 3-butenyloxy, 1-methylallyloxy, 2-pentenyloxy, 2-hexenyloxy, and the like.
  • the carboxy-substituted lower alkoxy group includes a carboxy - alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carboxymethoxy, 2 - carboxyethoxy, 1 -carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5 - carboxypentyloxy, 6-carboxyhexyloxy, 1 ,1-dimethyl-2-carboxyethoxy, 2-methyl - 3-carboxypropoxy, and the like.
  • the lower alkoxycarbonyl-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxy - carbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarbonylmethoxy, 3 - ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonyl - pentyloxy, 6-propoxycarbonylhexyloxy, 1 ,1 -dimethyl-2-butoxycarbonylethoxy, 2 methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxy - carbonylmethoxy, and the like.
  • the lower alkoxycarbonyl group includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, and the like.
  • the halogen-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which has 1 to 3 halogen substituents, for example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3 - chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5 - chloropentyloxy, 3-chloro-2-methylpropoxy, 5-bromohexyloxy, 5,6-dichloro - hexyloxy, 5-bromohexyloxy, 5,6-dichlorohexyloxy, and the like.
  • halogen substituents for
  • the hydroxy-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 hydroxy groups, for example, hydroxymethoxy, 2-hydroxy - ethoxy, 1 -hydroxyethoxy, 1 -hydroxypropoxy, 3-hydroxypropoxy, 2,3-dihydroxy- propoxy, 4-hydroxybutoxy, 1 ,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxy - pentyloxy, 5-hydroxypentyloxy, 6-hydroxyhexyloxy, 1-hydroxyisopropoxy, 2 - methyl-3-hydroxy ⁇ ropoxy, 2,3-dihydroxyethoxy, 3,4-dihydroxybutoxy, 5,6 - dihydroxyhexyloxy, and the like.
  • the phenyl-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety includes a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the phenyl moiety, for example, benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4 - phenylbutoxy, 1 ,1-dimethyl-2-phenylethoxy, 5-phenylpentyloxy, 6-phenyl - hexyloxy, 2-methyl-3-phenylpropoxy, 2-(3-methoxyphenyl)ethoxy,
  • the 1 ,3-dioxolanyl group having optionally a lower alkyl substituent includes a 1 ,3-dioxolanyl group which may optionally be substituted by 1 to 3 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 1 ,3-dioxolanyl, 2-methyl-1 ,3-dioxolanyl, 4-ethyl-1 ,3 - dioxolanyl, 2-propyl-1 ,3-dioxolanyl, 4-butyl-1 ,3-dioxolanyl, 2-pentyl-1 ,3 - dioxolanyl, 4-hexyl-1 ,3-dioxolanyl, 2,4-dimethyl-1 ,3-dioxolanyl, 2,4,5-trimethyl - 1 ,3-dioxolanyl, and the like.
  • the lower alkanoyl group includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, t-butylcarbonyl, hexanoyl, and the like.
  • the morpholino-substituted lower alkoxy group includes a morpholino-substituted alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, morpholinomethoxy, 2-morpholinoethoxy, 1-morpholinoethoxy, 3-(2 - morpholinyl)propoxy, 4-(3-morpholinyl)butoxy, 1 ,1 -dimethyl-2-(2-morpholinyl) - ethoxy, 5-morpholinopentyloxy, 6-morpholinohexyloxy, 2-methyl-3-morpholino - propoxy, and the like.
  • the phenyl-lower alkyl group includes a phenyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzyl, 2-phenylethyl, 1 -phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1 ,1-dimethyl-2 - phenylethyl, 2-methyl-3-phenylpropyl, and the like.
  • the phenyl-lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and may optionally have 1 to 3 straight chain or branched chain alkoxy substituents having 1 to 6 carbon atoms on the phenyl moiety, for example, in addition to the above mentioned phenyl-lower alkyl group, 2-(3 - methoxyphenyl)ethyl, 1-(4-methoxyphenyl)ethyl, 2-methoxbenzyl, 3-methoxy - benzyl, 4-methoxybenzyl, 3-(2-ethoxyphenyl)propyl, 4-(3-ethoxyphenyl)butyl, 1 ,1 -dimethyl-2-(4-ethoxyphenyl)ethyl, 5-(4-iso
  • the furyl-substituted lower alkyl group includes a furyl-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-furyl)methyl, 2-(3-furyl)ethyl, 1-(2-furyl)ethyl, 3-(2-furyl)propyl, 4-(3-furyl)butyl, 5-(2-furyl)pentyl, 6-(3-furyl) - hexyl, 1 ,1-dimethyl-2-(2-furyl)ethyl, 2-methyl-3-(3-furyl)propyl, and the like.
  • the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-furyl)methyl, 2-(3-furyl)ethyl, 1-(2-furyl)ethyl,
  • the lower alkoxy-lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethyl, 2-ethoxyethyl, 1-methoxyethyl, 3-methoxypropyl, 4 - ethoxybutyl, 6-propoxyhexyl, 5-isopropoxypentyl, 1 ,1-dimethyl-2-butoxyethyl, 2 methyl-3-tert-butoxypropyl, 2-pentyloxyethyl, hexyloxymethyl, and the like.
  • the alkenyl group includes a straight chain or branched chain alkenyl group with 1 to 3 double bonds having 2 to 12 carbon atoms, for example, vinyl, allyl, 3-methyl-2-butenyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2 - pentenyl, 2-hexenyl, 1-heptenyl, 1-octenyl, 1 -nonenyl, 1-decenyl, 1-undecenyl, 2-dodecenyl, 2-heptenyl, 3-heptenyl, 3-methyl-4-heptenyl, 2-methyl-5-heptenyl, 4-methyl-2-heptenyl, 3-methyl-l-heptenyl, 1 ,3-heptadienyl, 1 ,4-heptadienyl, 1,5 heptadienyl, 1 ,6-heptadienyl, 2,4-heptadienyl, 2-methyl-2,4-
  • the cycloalkyl-lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by a cycloalkyl group having 3 to 8 carbon atoms, for example, cyclohexylmethyl, 2-cyclopropylethyl, 1 -cyclobutylethyl, 3-cyclopentylpropyl, 4-cyclohexylbutyl, 2,2-dimethyl-3-cycloheptylpropyl, 5-cyclooctylpentyl, 6-cyclohexylhexyl, and the like.
  • the naphthyl-lower alkyl group includes a naphthyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, ⁇ -naphthylmethyl, ⁇ -naphthylmethyl,
  • the phenylthio-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenylthio-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and may optionally have 1 to 3 substituents of straight chain or branched chain alkoxy group having 1 to 3 carbon atoms on the phenyl moiety, for example, phenylthiomethyl, 2-phenylthioethyl, 1 - phenylthioethyl, 3-phenylthiopropyl, 4-phenylthiobutyl, 5-phenylthiopentyl, 6 - phenylthiohexyl, 1 ,1-dimethyl-2-phenylthioethyl, 2-methyl-3-phenylthiopropyl, (2-methoxyphenylthio)methyl, (3-methoxypheny
  • the phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenylsulfinylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and may optionally have 1 to 3 substituents of straight chain or branched chain alkoxy group having 1 to 6 carbon atoms on the phenyl moiety, for example, phenylsulfinylmethyl, 2-phenylsulfinylethyl, 1 - phenylsulfinylethyl, 3-phenylsulfinylpropyl, 4-phenylsulfinylbutyl, 5-phenyl - sulfinylpentyl, 6-phenylsulfinylhexyl, 1 ,1 -dimethyl-2-phenylsulfin
  • the phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenylsulfonyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents of straight chain or branched chain alkoxy group having 1 to 6 carbon atoms on the phenyl moiety, for example, phenylsulfonyl - methyl, 2-phenylsulfonylethyl, 1-phenylsulfonylethyl, 3-phenylsulfonylpropyl, 4 - phenylsulfonylbutyl, 5-phenylsulfonylpentyl, 6-phenylsulfonylhexyl, 1 ,1 - dimethyl-2-phenylsulfon
  • the 5- to 14-membered saturated or unsaturated hetero - monocyclic, heterobicyclic or heterotricyclic group having 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, thienyl, quinolyl, 1 ,4-dihydroquinolyl, benzothiazolyl, pyrazinyl, pyrimidyl, pyridazinyl, pyrrolyl, carbostyril, 3,4-dihydrocarbostyril, 1 ,2,3,4-tetrahydroquinolyl, indolyl, isoindolyl, indolinyl, benzimidazolyl, benzoxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, quinoxalinyl, cinnony
  • the lower alkyl group which is substituted by a 5- to 14 - membered saturated or unsaturated heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom includes, for example, pyrrolidinylmethy, 2 - piperidinylethyl, 3-piperazinylpropyl, 4-morpholinobutyl, (2-pyridyl)methyl, (3 - pyridyl)methyl, (2-thienyl)methyl, (3-quinolyl)methyl, 5-(6-quinolyl)pentyl, 6-(1 ,4 dihydro-2-quinolyl)hexyl, (2-benzothiazolyl)methyl, 2-(3-pyrazinyl)ethyl, 1-(2 - pyrimidyl)ethyl, 3-(3-pyridazinyl)propyl, 4-(2-pyrrolyl)butyl, 5-(
  • the phenoxy-substituted lower alkyl group includes a phenoxyalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, phenoxymethyl, 2 - phenoxyethyl, 1-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 5-phenoxy - pentyl, 6-phenoxyhexyl, 1 ,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxy - propyl, and the like.
  • the phenyl-lower alkoxy group which may optionally have an amino substituent having optionally a lower alkanoyl substituent on the phenyl moiety includes a phenylalkoxy group, wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents of amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4 - phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1 ,1-dimethyl-2-phenyl - ethoxy, 2-methyl-3-phenylpropoxy, 4-acetylaminobenzyloxy, 2-(2-propionyl - aminophenyl)ethoxy, 1 -(3-buty
  • the lower alkoxy-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethoxy, 3-methoxypropoxy, 4 - ethoxybutoxy, 6-propoxyhexyloxy, 5-isopropoxypentyloxy, 1 ,1 -dimethyl-2 - butoxyethoxy, 2-methyl-3-tert-butoxypropoxy, 2-pentyloxyethoxy, hexyloxy - methoxy, and the like.
  • the lower alkanoyloxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyloxymethyl, 2,2-dimethylpropionyloxy - methyl, propionyloxymethyl, 2-propionyloxyethyl, 1 -acetyloxyethyl, 1-butyryl - oxyethyl, 3-acetyloxypropyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-tert - butylcarbonyloxyhexyl, 1 ,1 -dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxy - propyl, and the like.
  • the halogen-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethyl, trichloro - methyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3 - chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloro - pentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, 5-bromo - hexyl, 5,6-dichlorohexyl, and the like.
  • the tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring includes a tetrazolyl group having optionally a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the tetrazole ring, for example, tetrazolyl, 1-methyltetrazolyl, 2-methyltetrazolyl, 5-ethyltetrazolyl, 5 propyltetrazolyl, 1-butyltetrazolyl, 2-pentyltetrazolyl, 1 -hexyltetrazolyl, and the like.
  • the phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy-substituted lower alkoxy group, hydroxy group, a halogen atom and a lower alkoxy group includes a phenyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, hydroxy group, a halogen atom and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3 - methylphenyl, 4-methylphenyl, 2-ethyl phenyl, 3-ethylphenyl, 4-ethylphenyl, 3 - isopropylphenyl,
  • the lower alkenyl group includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, vinyl, allyl, 2- butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl, 2-hexenyl, and the like.
  • the morpholinocarbonyl-lower alkoxy group includes a morpholinocarbonylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxyl group having 1 to 6 carbon atoms, for example, morpholinocarbonylmethoxy, 2-morpholinocarbonylethoxy, 1-morpholino - carbonylethoxy, 3-(2-morpholinocarbonyl)propoxy, 4-(3-morpholinocarbonyl) - butoxy, 1 ,1-dimethyl-2-(2-morpholinylcarbonyl)ethoxy, 5-morpholinylcarbonyl - pentyloxy, 6-morpholinocarbonylhexyloxy, 2-methyl-3-morpholinocarbonyl - propoxy, and the like.
  • morpholinocarbonylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxyl group having 1 to 6 carbon atoms, for example, morpholinocarbonylme
  • the morpholinocarbonyl-lower alkyl group includes a morpholinocarbonylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, morpholinocarbonylmethyl, 2-morpholinocarbonylethyl, 1 -morpholinocarbonyl - ethyl, 3-(2-morpholinocarbonyl)propyl, 4-(3-morpholinocarbonyl)butyl, 1 ,1 - dimethyl-2-(2-morpholinocarbonyl)ethyl, 5-morpholinocarbonylpentyl, 6 - morpholinocarbonylhexyl, 2-methyl-3-morpholinocarbonylpropyl, and the like.
  • morpholinocarbonylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, morpholinocarbonylmethyl,
  • the cycloalkylcarbonyl group includes a cycloalkylcarbonyl group having 3 to 8 carbon atoms in the cycloalkyl moiety, for example, cyclopropyl - carbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, and the like.
  • the phenyl-lower alkenylcarbonyl group includes a phenylalkenyl carbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenylcarbonyl moiety, for example, cinnamoyi, 4-phenyl-2-butenoyl, 4-phenyl • 3-butenoyl, 5-phenyl-4-pentenoyl, 5-phenyl-3-pentenoyl, 5-phenyl-2 - pentenoyi, 6-phenyl-5-hexenoyl, 6-phenyl-4-hexenoyl, 6-phenyl-3-hexenoyl, 6 - phenyl-2-hexenoyl, 2-methyl-4-phenyl-3-butenoyl, 2-methyl-cinnamoyl, 1 - methyl-cinnamoyl, and the like.
  • the 5- to 6-membered saturated heterocyclic group which is formed by combining R 6 and R 7 , R 9 and R 10 , R 40 and R 41 or R 52 and R 53 together with the adjacent nitrogen atom with or without being intervening with nitrogen atom or oxygen atom, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, and the like.
  • the above heterocyclic group having 1 to 3 substituents selected from hydroxy group, a lower alkyl group and a phenyl-lower alkyl group includes the above mentioned heterocyclic groups having 1 to 3 sustituents selected from hydroxy group, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 3-hydroxypyrrolidinyl, 2-hydroxypyrrolidinyl, 4-hydroxypiperidinyl, 3-hydroxypiperidinyl, 2-hydropiperidinyl, 3-hydroxypiperazinyl, 2-hydroxy - piperazinyl, 3-hydroxymorpholino, 2-hydroxymorpholino, 4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(3-phenylpropyl)pyrrolidinyl, 4-(4-pheny
  • the amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group includes an amino group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenylcarbonyl moiety, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, t-butyl - carbonylamino, hexanoylamino, cinnamoylamino, 4-phenyl-3-butenoylamino, 4-phenyl-2-butenoylamino
  • the amino group having optionally a lower alkanoyl substituent includes an amino group having optionally a substituent of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetyamino, propionylamino, butyrylamino, isobutyryl- amino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.
  • the alkylsufinyl group includes a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, butylsulfinyl, tert-butylsuifinyl, pentylsulfinyl, hexylsulfinyl, and the like.
  • the lower alkylthio group includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like.
  • the lower alkylsulfonyl group includes a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl, butysulfonyl, tert-butysulfonyl, pentylsulfonyl, hexylsulfonyl, and the like.
  • the lower alkanoyloxy group includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert - butylcarbonyloxy, hexanoyloxy, and the like.
  • the amino-substituted lower alkyl group having optionally a substituent selected from a lower alkylsulfonyl group and a lower alkanoyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 groups selected from a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1 - aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1 ,1 - dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, formylaminomethyl, 1-acetyl - aminoethyl, 2-propionylaminoethyl,
  • the 1 ,3-dioxolanyl-substituted lower alkyl group having optionally a lower alkyl substituent includes a 1 ,3-dioxolanyl-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (1 ,3-dioxolan-2-yl)methyl, 2-(1 ,3-dioxolan-4-yl)ethyl, 1-(1 ,3-dioxolan - 2-yl)ethyl, 3-(1 ,3-dioxolan-4-yl)propyl, 4-(1 ,3-dioxolan-2-yl)butyl, 2-(1 ,3 - dioxolan-2-
  • the alkanoyl-substituted lower alkyl group includes an alkanoylalkyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, formylmethyl, acetylmethyl, 2-propionylethyl, 1-butyrylethyl, 3 - isobutyrylpropyl, 4-pentanoylbutyl, 5-hexanoylhexyl, 6-tert-butylcarbonylhexyl,
  • the aminocarbonyl-substituted lower alkyl group which may optionally have a lower alkyl substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an aminocarbonyl having optionally 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonylmethyl, 2-aminocarbonylethyl, 1-aminocarbonylethyl, 3 - aminocarbonylpropyl, 4-aminocarbonylbutyl, 5-aminocarbonylpentyl, 6 - aminocarbonylhexyl, 1 ,1 -dimethyl-2-aminocarbonylethyl, 2-methyl-3-amino - carbonylpropyl, methylaminocarbonylmethyl, 1 -ethylaminocarbonylethyl, 2 - propylaminocarbonylethyl, 3-isopropyla
  • the lower alkoxycarbonyl-substituted lower alkenyl group includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy - carbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, 2 ⁇ methoxycarbonylvinyl, 2-ethoxycarbony vinyl, 3-propoxycarbonylallyl, 4-butoxy - carbonyl-2-butenyl, 4-pentyloxycarbonyl-3-butenyl, 3-hexyloxycarbonyl-1 - methylallyl, 5-isopropoxycarbonyl-2-pentenyl, 6-tert-butoxycarbonyl-2-hexenyl, and the like.
  • the aminocarbonyl-substituted lower alkenyl group which may optionally have a lower alkyl substituent includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms which is substitued by an aminocarbonyl group having optinally have 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 2 aminocarbonylvinyl, 3-aminocarbonylallyl, 4-aminocarbonyl-2-butenyl, 4 - aminocarbonyl-3-butenyl, 3-aminocarbonyl-1 -methylallyl, 5-aminocarbonyl-2 - pentenyl, 6-aminocarbonyl-2-hexenyl, 2-methylaminocarbonylvinyl, 3-ethyl - aminocarbonylallyl, 4-propylaminocarbonyl-2-butenyl, 4-isopropylamino - carbonyl-3-butenyl
  • the carboxy-substituted lower alkenyl group includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, 2-carboxyvinyl, 3-carboxyallyl, 4-carboxy-2-butenyl, 4-carboxy-3 - butenyl, 3-carboxy-1 -methylallyl, 5-carboxy-2-pentenyl, 6-carboxy-2-hexenyl, and the like.
  • the aminocarbonyl group having optionally a lower alkyl substituent includes an aminocarbonyl group which may optionally have 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethyl - aminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butyl- aminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexyl - aminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropyl - aminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexyl - aminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylamino - carbonyl, N-methyl-N
  • the phenylsulfonyl group having optionally a lower alkyl substituent includes a phenylsulfonyl group having optionally 1 to 3 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, phenylsulfonyl, 2-methyl phenylsulfonyl, 3 - methylphenylsulfonyl, 4-methylphenylsulfonyl, 2-ethylphenylsulfonyl, 3 - ethylphenylsulfonyl, 4-ethylphenylsulfonyl, 3-isopropylphenylsulfonyl, 4 - hexylphenylsulfonyl, 3,4-dimethylphenylsulfonyl, 2,5-dimethylphenylsulfonyl, 3,4,5-trimethylphenylsulfonyl, and the
  • the phenyl-lower alkenyl group includes a phenylalkenyl group wherein the alkenyl moiety is a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, styryl, cinnamyl, 4-phenyl-3-butenyl, 4 phenyl-2-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 5-phenyl-2 - pentenyl, 6-phenyl-5-hexenyl, 6-phenyl-4-hexenyl, 6-phenyl-3-hexenyl, 6 - phenyl-2-hexenyl, 2-methyl-4-phenyl-3-butenyl, 2-methyl-cinnamyl, 1 -methyl - cinnamyl, and the like.
  • the benzoyi group which may optionally have 1 to 3 substituents selected from a lower alkoxy group, a halogen atom, an amino group having optionally a lower alkanoyl substituent, and hydroxy group on the phenyl moiety includes a benzoyi group which may optinally have 1 to 3 substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a halogen atom, an amino group having optionally a straight chain or branched chain alkanoyl substituent having 1 to 6 carbon atoms and hydroxy group on the phenyl moiety, for example, benzoyi, 2-chlorobenzoyl, 3 - chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl, 3-fluorobenzoyl, 4-fluoro - benzoyi, 2-bromobenzoyl, 3-bromobenzoyl, 4-bromobenzoyl, 2-iodo
  • the amino-substituted lower alkanoyl group having optionally a lower alkanoyl substituent includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substitued by an amino group having optionally 1 to 2 substituents of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, 2-aminoacetyl, 3 - aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6 - aminohexanoyl, 2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl, 2 - acetylaminoacetyl, 2-acetylaminopropionyl, 3-propionylaminopropionyl, 3 - isopropionylaminopropionyl, 4-butyrylaminobutyryl, 5-pentanoyla
  • the amino-substituted sulfonyl group having optionally a lower alkyl substituent includes an aminosulfonyl group which may optionally have 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminosulfonyl, methylaminosulfonyl, ethylamino - sulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, butylaminosulfonyl, tert - butylaminosulfonyl, pentylaminosulfonyl, hexylaminosulfonyl, dimethylamino - sulfonyl, diethylaminosulfonyl, dipropylaminosulfonyl, dibutylaminosulfonyl, dibutylaminosulfonyl, dipentylaminos
  • the lower alkeneldioxy group includes a straight chain or branched chain alkylenedioxy group having 1 to 4 carbon atoms, for example, methylenedioxy, ethylenedioxy, trimethylenedioxy, tetramethylenendioxy, and the like.
  • the phenyl group having optionlly a lower alkoxy substituent includes a phenyl group which may optionally have 1 to 3 substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2 - ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-pentyl - oxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3-ethoxy-4-methoxy - phenyl, 2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5 - dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxy - phen
  • the 2,3-dihydro-1 H-indenyl-substituted lower alkyl group which may optionall have a substituent selected from oxo group, hydroxy group and silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1H-indenyl ring includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a 2,3-dihydro-1 H-indenyl group having optionally 1 to 3 substituents selected from oxo group, hydroxy group and a silyloxy group having 3 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2,3-dihydro-1 H-inden-2-yl) - methyl, 2-(2,3-dihydro-1 H-inden-1 -yl)ethyl, 1 -(2,3-dihydro-1 H-inden-3-yl)ethy
  • the silyloxy group having a lower alkyl substituent includes a silyloxy group being substituted by three straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, trimethylsilyloxy, triethyl - silyloxy, triisopropylsilyloxy, tributylsilyloxy, tri-tert-butylsilyloxy, tripentylsilyloxy, trihexylsilyloxy, dimethyl, tert-butylsilyloxy, and the like.
  • the phenyl group having optionally a substituent selected from a lower alkoxy group and a halogen atom on the phenyl ring includes a phenyl group which may optionaly be substituted by 1 to 3 groups selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a halogen atom, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4 - methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4 - isopropoxyphenyl, 4-pentyloxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4 - diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxy
  • the saturated or unsaturated 5- to 6-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, thienyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, imidazolidinyl, pyrazolyl, imidazolyl, pyrazolidinyl, 1 ,3,4-oxadiazolyl, 1 ,2,4 - triazolyl, 1 ,2,3,4-tetrazolyl, 1 ,3,4-triazolyl, 1 ,2,4-oxadiazolyl, furyl, pyrrolinyl, oxazolyl, isoxazolyl, thiazolyl, thiazolidinyl, 1 ,2,3,5-oxathiadiazolyl,
  • the lower alkyl group substitued by a 5- to 6-membered saturated or unsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by the above mentioned heterocyclic group, for example, pyrrolidinylmethyl, 2 - piperidinylethyl, 3-piperazinylpropyl, 4-morpholinobutyl, (2-pyridyl)methyl, (3 - pyridyl)methyl, (2-thienyl)methyl, 2-(3-pyrazinyl)ethyl, 1-(2-pyrimidyl)ethyl, 3-(3 - pyridazinyl)propyl, 4-(2-pyrrolyl)butyl, 4-(4-imidazolidinyl)butyl, (2-imidazolyl)- methyl, (3-pyrazolyl)methyl, 2-(
  • the lower alkenyl group substituted by a 5- to 14-membered saturated or unsaturated heteromonocylic, heterobicyclic or heterothcyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom includes the above mentioned heterocyclic group-substituted alkenyl group wherein the alkenyl moiety is a straight chain or branched chain alkenyl group with 1 to 2 double bounds having 2 to 6 carbon atoms, for example, 2-benzofurylvinyl, 3-benzofuryl-2-propenyl, 4-benzofuryl-3-butenyl, 3 - benzofuryl-2-butenyl, 2-methyl-3-benzofuryl-2-propenyl, 5-benzofuryl-4 - petenyl, 5-benzofuryl-2-pentenyl, 4-benzofuryl-3-pentenyl, 6-benzofuryl-5 - hexenyl, 6-benzofuryl-4-hexenyl, 6-
  • the phenyl-lower alkoxycarbonyl group includes a phenylalkoxy - carbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1 -phenyl - ethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenyl - pentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1 ,1 -dimethyl-2-phenylethoxy - carbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.
  • the lower alkoxycarbonyloxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by alkoxycarbonyloxy group wherein the alkoxy moiety is a a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms , for example, methoxycarbonyloxymethyl, ethoxycarbonyloxy - methyl, 2-ethoxycarbonyloxyethyl, 1 -ethoxycarbonyloxyethyl, 3-methoxy - carbonyloxypropyl, 4-ethoxycarbonyloxybutyl, 6-propoxycarbonyloxyhexyl, 5 - isopropoxycarbonyloxypentyl, 1 ,1 -dimethyl-2-butoxycarbonyloxyethyl, 2-methyl • 3-tert-butoxycarbonyloxypropyl, 2-pentyloxycarbonyloxyethyl, hex
  • the benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring includes a straight chain or branched chain alkyl group having 1 to 6 carbon atom, which is substituted by a benzoyi group wherein the phenyl ring may optionally have 1 to 3 halogen substituents, for example, benzoylmethyl.
  • the amino group having optionally a lower alkanoyl substituent includes an amino group which may optionally have a substituent of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, t-butylcarbonylamino, hexanoylamino, and the like.
  • the present invention specifically includes the following compounds.
  • R 1 , R 3 , R 4 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lower alkyl group
  • R 4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lower alkyl group
  • R 4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro - 1 H-indenyl ring
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkenyl group, R 2 is hydrogen atom, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are the same as defined above), a lower alkenyloxy group, nitro
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is hydrogen atom
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenylthio-substitued lower alkyl group which may optinally have a lower alkoxy substituent on the phenyl moiety
  • m, n, and r are the same as defined above, or a salt thereof.
  • R 6 A quinoxaline derivative of the formula (1), wherein R 1 is a halogen atom or a lower alkyl group, R 2 is hydrogen atom, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is hydrogen atom, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula: -A 5 -CR 42 R 3 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are the same as defined above
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a 2,3 - dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring
  • m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a group of the formula:
  • R is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 4 0R 41 (in which A 4 , R 4 ° and R 41 are the same as defined above), a lower alkeny
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is a morpholino-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are the same
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is a morpholino-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is a morpholino-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is a morpholino-substituted lower alkyl group, R 3 and R 4 combine together with the nitrogen atom to form 1 ,2,3,4 - tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenylsulfinyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula: -A ⁇ -CR ⁇ R ⁇ R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
  • R 2 , m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is hydrogen atom, R 3 is a lower alkyl group, R 4 is a naphthyl-lower alkyl group, and R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 is hydrogen atom
  • R 3 is hydrogen atom
  • R 4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 is hydrogen atom
  • R 3 is a lower alkyl group
  • R 4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group and R 2 , R 3 , R 4 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a phenyl - lower alkoxycarbonyl group and R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl ring selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 4 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group and R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl ring selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -0-A 4 -CO-NR 4 OR 4 1 (in which A 4 , R 40 and R 41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 3 is a phenyl - lower alkoxycarbonyl group, R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 3 is a lower alkanoyloxy-substituted lower alkyl group, R 4 is a group of the formula: -A 5 -CR 4 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 41 (in which A 4 , R 40 and R 41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R 1 , R 3 , R 4 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lower alkoxy - lower alkyl group
  • R 4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 42 , R 43 and R 44 are the same as defined above), and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lower alkoxy-lower alkyl group
  • R 4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lower alkoxycarbonyloxy-substituted lower alkyl group
  • R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - calbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally
  • R 1 , R 2 , m, n and r are the same as the same, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R 4 is a cycloalkyl-lower alkyl group, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lower alkoxycarbonyloxy-substituted lower alkyl group
  • R 4 is a cycloalkyl-lower alkyl group
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lowe alkanoyl-substituted lower alkyl group
  • R 4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a lower alkoxycarbonyloxy-substituted lower alkyl group
  • R 4 is a phenoxy-substituted lower alkyl group
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula: -E-NR 52 R 53 (in which E, R 52 and R 53 are the same as defined above),
  • R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group
  • R 3 is a group of the formula: -E-NR 52 R 53 (in which E, R 52 and R 53 are the same as defined above), R 4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula: -E-NR 52 R 53 (in which E, R 52 and R 53 are the same as defined above), R 4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula: -E-NR 52 R 53 (in which E, R 52 and R 53 are the same as defined above), R 4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring
  • R 4 is a phenoxy-substituted lower alkyl group
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula: -E-NR 52 R 53 (in which E, R 52 and R 53 are the same as defined above), R 4 is a phenoxy-substituted lower alkyl group, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula: -E-NR 52 R 53 (in which E, R 52 and R 53 are the same as defined above)
  • R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above)
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring
  • R 4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula: -E-NR 5 R 53 (in which E, R 52 and R 53 are the same as defined above), R 4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro -
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring
  • R 4 is a group of the formula:
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 4 is a group of the formula:
  • R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl - lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R 1 , R 3 ,
  • R 4 , m, n and r are the same as defined above, or a salt thereof.
  • R 4 is a lower alkenyl group, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula:
  • R 4 is a cycloalkyl-lower alkyl group, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 4 is a naphthyl-lower alkyl group, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula:
  • R 4 is a phenylthio - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R 1 , R 2 , m, n and r are the same as defined above, or a sa
  • R 3 is a group of the formula:
  • R 4 is a phenylsulfinyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 3 is a group of the formula: — 54
  • R 4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 4 is a phenoxy - substituted lower alkyl group, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 4 is a group of the formula:
  • R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 4 is a 2,3-dihydro-1 H - indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R 1 , R 2 , m, n and r are the same as defined above, or a salt thereof.
  • R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a lower alkenyl group
  • m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a cycloalkyl - lower alkyl group
  • m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is hydrogen atom, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenylthio - substitued lower alkyl group which may optinally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is hydrogen atom, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is hydrogen atom, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a lower alkyl group having optionally a halogen substituent, R 3 is hydrogen atom or a lower alkyl group, R 4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a lower alkyl group having optionally a halogen substituent, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a lower alkyl group having optionally a halogen substituent, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a lower alkyl group having optionally a halogen substituent, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a lower alkyl group having optionally a halogen substituent, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is phenyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is phenyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is phenyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is phenyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is phenyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is phenyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a 2,3-dihydro-1 H - indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring
  • m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is phenyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is phenyl group
  • R 3 and R 4 combine together with the nitrogen atom to form 1 ,2,3,4 - tetrahydroisoquinolyl group which may optionally have a lower alkoxy group)
  • m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a morpholino-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a morpholino-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a morpholino-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (A 5 , R 42 , R 43 and R 44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro - 1 H-indenyl ring
  • m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is a morpholino-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A 4 -
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety
  • m, n and r are the same as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is hydrogen atom or a lower alkyl group
  • R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R 2 is an imidazolyl-substituted lower alkyl group, R 3 is hydrogen atom or a lower alkyl group, R 4 is a group of the formula:
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula: _ A R 54
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 5 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group. of the formula: (in which R 54 is hydrogen atom or a lower alkyl group and A is the same as defined
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and R 2 , m, n, and r are as
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a lower alkenyl group; and
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a cycloalkyl-lower alkyl group; and
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a naphthyl-lower alkyl group; and
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 5 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; and
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula: _ A R 54
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; and
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; and
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group; and
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula: _A R 54
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a group of the formula: -As-CR ⁇ R ⁇ R 44 (in which A 5 ,
  • R 42 , R 43 and R 44 are as defined above); and R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 1 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula: — A R 54
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring
  • R 2 , m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having otionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above,
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is hydrogen atom; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is hydrogen atom; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula: (in which R
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is hydrogen atom; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxy - carbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is hydrogen atom; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxy - carbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R53 are as defined above), or a group of the formula:
  • R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (in which A 5 , R 42 , R 43 and R 44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above,
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E - N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above),
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above),
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above),
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above),
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above),
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above),
  • R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (in which A 5 , R 42 , R 43 and R 44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring
  • m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above,
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a hal
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 5 )(R 53 ) (in which
  • R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is phenyl group; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 5 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula: (in
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is phenyl group; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is phenyl group; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (in which A 5 , R 42 , R 43 and R 44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is phenyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined above), or a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above,
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substit
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 5 )(R 53 ) (in which E, R 52 and R 53 are as defined above
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is a morpholino-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is a morpholino-substituted lower alkyl group; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 5 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is an imidazolyl-substituted lower alkyl group; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • a quinoxaline derivative of the formula (1) wherein R 1 is a halogen atom or a lower alkyl group; R 2 is an imidazolyl-substituted lower alkyl group; R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 )
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 5 )(R 53 ) (in which E, R 52 and R 53 are as
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (in which A 5 , R 42 , R 43 and R 44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a halogen atom or a lower alkyl group
  • R 2 is an imidazolyl-substituted lower alkyl group
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which E, R 52 and R 53 are as defined
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above,
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in
  • R 4 is a group of the formula: -A 5 -CR 42 R 43 R 44 (in which A 5 , R 42 , R 43 and R 44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is hydrogen atom
  • R 3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R 52 )(R 53 ) (in which
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above
  • R 4 is a 2,3-dihydro-1H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2, 3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxy - carbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A 4 -CO-NR 40 R 41 (in which A 4 , R 40 and R 41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above,
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy- carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula:
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
  • R 1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent
  • R 2 is a lower alkyl group having optionally a halogen substituent
  • R 3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -
  • R 54 is hydrogen atom or a lower alkyl group and A is the same as defined above);
  • R 4 is a group of the formula:

Abstract

Quinoxaline derivatives of formula (1), and salts thereof, which have excellent antidiabetic activity, and an antidiabetic agent comprising as an active ingredient the quinoxaline derivative or a pharmaceutically acceptable salt thereof.

Description

D E S C R I P T I O N
QUINOXALINE DERIVATIVE AS ANTIDIABETIC AGENT
Technical Field
The present invention relates to an antidiabetic agent. Background Art
Various quinoxaline derivatives have been known. For example, BE-764998 (= JP-A-46-4377) discloses that the following sulfonylureas are useful as hypoglycemic agents.
R-CO-NH S02NHCONHR2
Figure imgf000003_0001
wherein R is a group of the formula:
Figure imgf000003_0002
and R2 is alkyl, alkenyl, cycloalkyl, etc. Said compounds are similar to the compounds of this invention in the basic structure and also in the pharmacological activity but are distinguished from the compounds of this invention in the substituent on the phenyl ring in the substituent -CONR3R4 at 2 position of quinoxaline ring.
DD-273254-A discloses selective reduction of quinoxaline-di-N - oxide derivatives of the formula:
Figure imgf000003_0003
wherein R-- is H, Cl, methyl, or methoxy, and R2 is OH, alkoxy or β - hydroxyethylamino, to give the corresponding N-4-monoxides which are useful as an intermediate for pharmaceuticals and pesticides.
DT-2410852 (= JP-A-50-29583) discloses N-tetrazolyl - quinoxaline-2-carboxamides of the formula:
Figure imgf000004_0001
wherein A is -N=CR2- etc., R is H, halogen, alkyl, OR3, NR4R5, etc., and R6 and R7 are H, halogen, alkyl, OR3, NR4R5, etc., which are useful for treating disorders such as asthma, hay-fever, urticaria, eczema or atopic dermatitis.
EP-23785 discloses substituted alkoxy-phenoxy-quinoxaline(s), N oxide(s) thereof of the formula:
Figure imgf000004_0002
wherein A, B, D, E, J, U and V are H, halogen, nitro, CN, amino, mono- or di - substituted amino, alkyl, alkoxy, carbamoyi, etc.; Y and X are O or S; R1 and R2 are H, alkyl, alkenyl, etc.; and W is CN, CSNH , etc., which are useful as pre- and post-emergence selective herbicides. EP-26622 discloses also similar quinoxalinyl-amino-phenoxyalkanoic acids which are useful as pre- and post - emergence selective herbicides.
Heterocycles, Vol. 26, No. 3, 1987, pp. 699-711 discloses substituted 2-quinoxalinecarboxamides and their N-oxides of the formula:
Figure imgf000004_0003
(0)m
wherein R is H or methyl, n is 0 or an integer of 1 to 4, 1 and m are 0 or 1 , but no pharmacological activity of these compound is mentioned.
J. Chem. Eng. Data, vol. 29, No. 2, pp. 229-231 (1984) discloses quinoxaline compounds of the formula:
Figure imgf000005_0001
wherein I and m are 0 or 1 , and R is 2-imidazolyl, 3-indolyl, etc. which have antibacterial activity.
DD-284585-A discloses quinoxaline-1 ,4-di-N-oxides of the formula:
Figure imgf000005_0002
wherein R1 is H or optionally substituted alkyl, and R2 is H, optionally substituted alkyl, or hydroxyethylcarbamoyl, which are useful as a medicinal feedstuff to protect piglets from gastro-intestinal disorders.
BE-721725 discloses 3-carboxamidoquinoxaline-di-N-(1 ,4) - oxides of the formula:
Figure imgf000005_0003
wherein R-| is H, alkyl, alkoxy, or Cl; R and R3 are H, optionally substituted alkyl, or may form with N a 5- or 6- membered heterocyclic ring; X is 0 or S; and R4 is optionally substituted alkyl or optionally substituted phenyl, which have antibacterial activity. Similar compounds are also disclosed in many literatures such as BE-721726, BE-721728, BE-738246, BE-742970, DT-2012743, NL - 7305048, BE-846532, GB-1308370, JP-B-46-23264, JP-B-45-24988, and JP-B • 45-24989. NL-7206031 discloses 2-formyl-3-carbamoyl-quinoxaline 1 ,4 - dioxides of the formula:
Figure imgf000006_0001
wherein R-- and R2 are H, optionally substituted aliphatic or cycloaliphatic group, or form a 5- to 7-membered ring optionally containing 0 or S, Z is NOH or NNHC(Y)R3, which have antimicrobial activity. Similar compounds are also disclosed in many literatures such as BE-856771 , DT-2639429, DT-2656783, EP-1618, EP-73390, DE-3230273-A, BE-824065, DT-2501492, BE-828745, US-3948911 , US-4039540, DD-268127, DD-268942-A, JP-A-62-120371 , JP-A - 62-123178, EP-288628-A, JP-A-60-120815, BE-856771 , and BE-753582. DE-3324908-A discloses 2-(N-(2-hydroxyethyl)carbamoyl)-3 - methylquinoxaline 1 ,4-di-N-oxide of the formula:
O
Figure imgf000006_0002
which is useful as animal growth promoters. Similar compounds are also disclosed in other many literatures such as EP-142093-A, DT-2907174, JP-A -
50-082217, GB-2038824, JP-A-62- 174061 , and JP-A-62-149670. NL-7206601 discloses 2,3-disubstituted quinoxaline-1 ,4-dioxides of the formula:
Figure imgf000006_0003
wherein R1 is phenyl optionally substituted by alkyl, alkoxy, halogen or CF3, and R2 is -CONR3R4 where R3 and R4 are H or alkyl or form together alkylene optionally containing O, S or N heteroatom, which are useful as bactericides and amoebicides. Similar compounds are also disclosed in BE-763377, DT - 2228802, and BE-904482.
EP-12725 discloses quinoxaline di-N-oxides of the formula:
Figure imgf000007_0001
wherein R1 is H or alkyl; R2 and R3 are alkyl or NR2R3 forms 4-5C heterocyclic ring optionally substituted by alkyl, and R4 is H, methoxy, methylthio, OH, F, Cl, Br or CN, which are useful as broad-spectrum antimicrobial agents, esp. as veterinary medicaments, and animal growth promoters. Similar compounds are also disclosed in DT-2701707. CH-619456 discloses 6-phenylthio-quinoxaline-1 ,4-dioxide derivatives of the formula:
Figure imgf000007_0002
wherein one of A and B is methyl, and the other is -CONHCH2CH2OH, which are useful as animal growth stimulants. Similar compounds are also disclosed in CH-619457 and CH-630908. DT-2052359 discloses quinoxaline 1 ,4-dioxides of the formula:
Figure imgf000007_0003
wherein R-* and R2 are each H, alkyl or alkoxy, or form together methyienedioxy; R3 is H, optionally unsaturated aliphatic residue (optionally substituted by CN, COOH, carbamoyi, alkylamino, etc.), a 5- or 6-membered cycloaliphatic residue (optionally substituted by alkyl), aryialkyi or furfuryl; R is H, or NR3R4 is optionally unsaturated 5- or 6-membered heterocyclic ring optionally substituted by alkyl; and R5 is optionally substituted and optionally unsaturated aliphatic, cycloaliphatic, araliphatic aromatic or heterocyclic residue, which have antiprotozoal and antibacterial activity. Similar compounds are also disclosed in DT-2052279.
DT-2120501 discloses 3-substituted quinoxaline-2-carboxamido - 1 ,4-dioxides of the formula:
Figure imgf000008_0001
wherein X is H, methyl, methoxy, CF3, F, Cl, or Br; Y is alkylthio, alkylsulfinyl, or alkylsulfonyl; R' is H or alkyl; and R" is H or alkyl optionally substituted by amino alkylamino, dialkylamino, pyrrolidino, piperidino, etc., which are useful as broad spectrum antibacterial agents, growth stimulants especially for pigs and poultry. Similar compounds are also disclosed in BE-764088, BE-773396, and DT-2212932. US-3185688 discloses quinoxaline derivatives of the formula:
Figure imgf000008_0002
wherein Z is NR(CH2)nNR1R2, NR(CH2)nOalkyl, NR(CH2)nSalkyl; X and R are H or alkyl; R-* and R2 are alkyl, or NR1R2 is morpholino, piperidino, pyrrolidino; and n is 2 - 4, which are useful as tranquilizers. Similar compounds are also disclosed in US-3192212 and FR-2211006.
Disclosure of Invention
The antidiabetic agent of the present invention comprises as an active ingredient at least one of quinoxaline derivatives of the formula (1):
Figure imgf000009_0001
wherein R1 is hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, a lower alkyl group having optionally a halogen substituent, phenyl group, a morpholino-substituted lower alkyl group or an imidazolyl-substituted lower alkyl group, n and m are each 0 or 1 , r is 1 or 2, R3 and R4 are the same or different and each a) hydrogen atom; b) a lower alkyl group; c) a phenyl-lower alkoxycarbonyl group; d) a lower alkanoyloxy-substituted lower alkyl group; e) a lower alkanoyl group; f) a lower alkoxycarbonyl group; g) a lower alkoxy-lower alkyl group; h) a phenoxycarbonyl group; i) a lower alkanoyl-substituted lower alkyl group; j) a lower alkoxycarbonyloxy-substituted lower alkyl group; k) a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring; I) a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); m) a group of the formula:
Figure imgf000010_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); n) a group of the formula:
Figure imgf000010_0002
(in which A is the same as defined above, p is an integer of 1 to 3, R5 is hydrogen atom, a lower alkoxy-substituted lower alkoxy group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, a halogen atom, nitro group, hydroxy group, a lower alkyl group having optionally a hydroxy substituent, a lower alkenyloxy group, a carboxyl-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a lower alkoxycarbonyl group, a halogen-substituted lower alkoxy group, a hydroxy - substituted lower alkoxy group, a phenyl-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety, a 1 ,3-dioxolanyl group having optionally a lower alkyl substituent, a lower alkanoyl group, a morpholino-substituted lower alkoxy group, a morpholino-substituted lower alkyl group, a morpholinocarbonyl group or a group of the formula: -Y-A CONR6R7 (in which A*| is a lower alkylene group, Y is a group of the formula: -O- or a group of the formula: -NH-, R6 and R7 are the same or different and each hydrogen atom, a lower alkyl group having optionally a hydroxy substituent, a phenyl-lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, a furyl-substituted lower alkyl group, or a lower alkoxy-substituted lower alkyl group, or R6 and R7 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with nitrogen atom or oxygen atom, said heterocyclic group having optionally 1 to 3 substituents selected from hydroxy group, a lower alkyl group and a phenyl-lower alkyl group)); o) a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O - A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; p) an alkenyl group; q) a cycloalkyl-lower alkyl group; r) a naphthyl-lower alkyl group; s) a phenylthio-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; t) a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; u) a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; v) a phenoxy-substituted lower alkyl group; w) a group of the formula:
Figure imgf000011_0001
(in which q is an integer of 1 to 3, a group of the formula:
is a lower alkyl group substitu -tedQ by a 5- to 14-membered saturated or unsaturated heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, R8 substitutes on the above heterocyclic group, and is hydrogen atom, oxo group, a lower alkyl group having optionally a hydroxy substituent, a halogen atom, nitro group, a lower alkoxy group, cyano group, a lower alkoxycarbonyl group, a phenyl-lower alkoxy group having optionally an amino group having optionally a lower alkanoyl substituent on the phenyl moiety, a carboxyl - substituted lower alkoxy group, carboxyl group, a lower alkoxycarbonyl - substituted lower alkoxy group, hydroxy group, a lower alkoxy-substituted lower alkoxy group, a lower alkenyloxy group, a lower alkanoyloxy-substituted lower alkyl group, a halogen-substituted lower alkyl group, a lower alkanoyl group, a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy-substituted lower alkoxy group, hydroxy group, a halogen atom and a lower alkoxy group on the phenyl moiety, a lower alkenyl group, a morpholinocarbonyl-lower alkoxy group, a lower alkylsufinyl group, an amino - substituted lower alkyl group having optionally a substituent selected from a lower alkylsulfonyl group and a lower alkanoyl group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkanoyloxy group, a 1 ,3-dioxolanyl - substituted lower alkyl group having optionally a lower alkyl substituent, a lower alkanoyl-substituted lower alkyl group, an aminocarbonyl-substituted lower alkyl group having optionally a lower alkyl substituent, a lower alkoxycarbonyl-substituted lower alkenyl group, an aminocarbonyl-substituted lower alkenyl group having optionally a lower alkyl substituent, a carboxyl - substituted lower alkenyl group, benzoyl group, a lower alkoxy-lower alkyl group, a group of the formula:
Figure imgf000012_0001
(in which s is an integer of 1 to 3, a group of the formula:
is a 5- to 6-membered saturated o -r u©nsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R45 bonds to said heterocyclic group and is hydrogen atom, a lower alkyl group, a lower alkoxy-substituted lower alkyl group, phenyl group or oxo group), a group of the formula:
Figure imgf000012_0002
(in which t is an integer of 1 to 3, a group of the formula:
Figure imgf000013_0001
is a lower alkyl group substituted by a 5- to 6-membered saturated or unsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R46 bonds to said heterocyclic group and is hydrogen atom, a lower alkyl group or oxo group), or a group of the formula: -(C=0)*NR9R1° (in which I is 0 or 1 , R9 and R10 are the same or different and each hydrogen atom, a lower alkanoyl group, a lower alkyl group, a morpholinocarbonyl-lower alkyl group, a cycloalkylcarbonyl group, a phenyl - lower alkenylcarbonyl group, a lower alkylsulfonyl group, an aminocarbonyl group having optionally a lower alkyl substituent, a phenylsulfonyl group having optionally a lower alkyl substituent on the phenyl moiety, a phenyl-lower alkenyl group, a benzoyl group having optionally 1 to 3 substituents selected from a halogen atom, a lower alkoxy group, an amino group having optionally a lower alkanoyl substituent and hydroxy group on the phenyl moiety, an amino - substituted lower alkanoyl group having optionally a lower alkanoyl substituent, an amino-substituted sulfonyl group having optionally a lower alkyl substituent, a phenyl-lower alkyl group, phenyl group, or an amino group having optionally a lower alkanoyl substituent, or R9 and R10 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom)); x) a group of the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); y) a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1H-indenyl ring; or z) a group of the formula:
Figure imgf000013_0002
(in which u is an integer of 1 to 3, a group of the formula:
Figure imgf000014_0001
is a lower alkenyl group substituted by a 5- to 14-membered saturated or unsaturated, heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R47 bonds on said heterocyclic group and is hydrogen atom, a halogen - substituted lower alkyl group, oxo group, a halogen atom, a lower alkoxy group, a lower alkyl group, a lower alkoxycarbonyl group, carboxyl group, an aminocarbonyl group having optionally a lower alkyl substituent, an amino group having optionally a lower alkanoyl substituent, a phenyl group having optionally a substituent selected from a lower alkoxy group and a halogen atom on the phenyl moiety, or a group of the formula:
Figure imgf000014_0002
(in which A6, R45 and s are the same as defined above)), or R3 and R4 may combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, or a salt thereof.
The present invention provides also novel quinoxaline derivatives of the formula (1 ) as described above wherein all the symbols are the same as defined above except that n is 0 and the group R5 excludes hydrogen atom and further provided that when R1 is hydrogen atom, R2 is methyl group, R3 is hydrogen atom, and m is 0, then R4 is not 2-(imidazol-2-yl)ethyl, 2-(indol-3 - yl)ethyl, or sec-butyl, and a salt thereof.
According to the diseases determination by WHO, diabetes is caused by the absolute lack of the secretion of insulin and arises either acutely or subacutely, and includes, insulin dependent diabetes mellitus (IDDM) which requires the insulin-treatment, non insulin dependent diabetes mellitus
(NIDDM) which does not always require insulin-treatment, malnutrition-related diabetes mellitus (MRDM), other complications accompanied with other diseases.
Among the above, a cause of IDDM is estimated to be the destruction of pancreatis β-cells by auto-immune system. The pancreatis β - cells are considered to be destroyed by HLA antigen, cytokine virus, etc. (cf.
Koji NAKANISHI, Tetsuro KOBAYASHI, Mitsuru HARA; Tonyobyogaku (Diabetology) 1989: edited by Mikinori KOSAKA, Yasuo AKANUMA, Shindan- to-Chiryo sha, 1989, pages 226-244). On the other hand, the cause of NIDDM is estimated to be (i) congenital anomaly in pancreatin, i.e. anomaly in adaptability to the increase in insulin consumption, or (ii) disorder in insulin activity induced by various factors such as aging, obesity, stress, etc. (Hiroo IMURA; Tonyobyogaku-no-Shinpo (Progress in Diabetology) 1989, No. 23, edited by Japan Diabetology Association, Shindan-to-Chiryo sha, 1989, pages 1 to 12). However, the crisis of diabetes is not simple but happens in complicated situation, such as hereditary factors, environmental factors, etc., and it has not been clarified yet.
In viewpoint of the tissue of the patient of NIDDM, the important causes of hyperglycemia is considered to be the decrease in the uptake of glucose at the peripheral tissue, especially at the muscle, and the increase in glucose secretion at the liver. Hitherto, the most common drug therapy for diabetes is treatment with insulin or sulfonylurea agent (agent for promotion of insulin secretion), which are both based on the supplement of insulin, but these treatment have difficulty in strict blood glucose level control, and sometimes they induce hyperinsulin serum or hypoglycemia. Accordingly, it has been considered that a compound which promotes the uptake of glucose at the muscle without promoting the secretion of insulin would be a new kind of hypoglycemic agent without hyperinsulinism nor hypoglycemia and would be useful for treatment of diabetes. The quinoxaline derivatives of the above formula (1 ) and salts thereof (hereinafter referred to as the compounds of the present invention) promote the uptake of 2-deoxyglucose (2DG) against L6 cells, cell line of rat striated muscle (muscular cells) and also promote the consumption of glucose by which they show hypoglycemic activity. Especially, the compounds of the present invention show hypoglycemic activity in db/db mice and KK-Ay mice, which are diabetic animal model (L. Herberg, D.L. Coleman: Metabolism, vol. 26, No. 1 (January), 1977, pp. 59-99). The compounds of the present invention promote the uptake of glucose at the muscle and do not affect the insulin secretion and the glucose release at the liver so that they do not show acute hypoglycemic activity and do not affect oral glucose tolerance test.
Accordingly, the antidiabetic agent of the present invention is useful for treatment of diabetes and diabetic complications such as diabetic blood vessel disorder, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, etc.
Each group in the above formula (1) specially means the following groups. The lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl, etc.
The halogen atom is fluorine atom, chlorine atom, bromine atom or iodine atom. The lower alkyl group having optionally a halogen substituent includes, for example, in addition to the above mentioned lower alkyl groups, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms having optionally 1 to 3 halogen substituents, such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromo - methyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl,
2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2 • methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, 5-bromohexyl, 5,6-dichloro - hexyl, etc.
The morpholino-substituted lower alkyl group includes a morpholino-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, morpholinomethyl, 2-morpholinoethyl, 1-morpholinoethyl, 3-(2-morpholinyl) - propyl, 4-(3-morpholinyl)butyl, 1 ,1-dimethyl-2-(2-morpholinyl)ethyl, 5- morpholinopentyl, 6-morpholinohexyl, 2-methyl-3-morpholinopropyl, etc.
The imidazolyl-substituted lower alkyl group includes an imidazolyl-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (1 - imidazolyl)methyl, 2-(1-imidazolyl)ethyl, 1-(2-imidazolyl)ethyl, 3-(4-imidazolyl) - propyl, 4-(5-imidazolyl)butyl, 1 ,1-dimethyl-2-(2-imidazolyl)ethyl, 5-(4 - imidazoly pentyl, 6-(1-imidazolyl)hexyl, 2-methyl-3-(1-imidazolyl)propyl, etc. The lower alkylene group includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1 - methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene, etc.
The lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.
The amino group being optionally substituted by a lower alkyl group includes an amino group which may optionally be substituted by 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N - butylamino, N-methyl-N-hexylamino, and the like.
The lower alkyl group having optionally a hydroxy substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 1-hydroxyisopropyl, 3-hydroxy - propyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1 ,1-dimethyl-2-hydroxyethyl, 5,5,4 - trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 2-methyl-3-hydroxypropyl, 2,3-dihydroxyethyl, 3,4-dihydroxybutyl, 5,6-dihydroxyhexyl, and the like.
The lower alkenyloxy group includes a straight chain or branched chain alkenyloxy group having 2 to 6 carbon atoms, for example, allyloxy, 2 - butenyloxy, 3-butenyloxy, 1-methylallyloxy, 2-pentenyloxy, 2-hexenyloxy, and the like.
The carboxy-substituted lower alkoxy group includes a carboxy - alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carboxymethoxy, 2 - carboxyethoxy, 1 -carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5 - carboxypentyloxy, 6-carboxyhexyloxy, 1 ,1-dimethyl-2-carboxyethoxy, 2-methyl - 3-carboxypropoxy, and the like.
The lower alkoxycarbonyl-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxy - carbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarbonylmethoxy, 3 - ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonyl - pentyloxy, 6-propoxycarbonylhexyloxy, 1 ,1 -dimethyl-2-butoxycarbonylethoxy, 2 methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxy - carbonylmethoxy, and the like.
The lower alkoxycarbonyl group includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, and the like.
The halogen-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which has 1 to 3 halogen substituents, for example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3 - chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5 - chloropentyloxy, 3-chloro-2-methylpropoxy, 5-bromohexyloxy, 5,6-dichloro - hexyloxy, 5-bromohexyloxy, 5,6-dichlorohexyloxy, and the like. The hydroxy-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 hydroxy groups, for example, hydroxymethoxy, 2-hydroxy - ethoxy, 1 -hydroxyethoxy, 1 -hydroxypropoxy, 3-hydroxypropoxy, 2,3-dihydroxy- propoxy, 4-hydroxybutoxy, 1 ,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxy - pentyloxy, 5-hydroxypentyloxy, 6-hydroxyhexyloxy, 1-hydroxyisopropoxy, 2 - methyl-3-hydroxyρropoxy, 2,3-dihydroxyethoxy, 3,4-dihydroxybutoxy, 5,6 - dihydroxyhexyloxy, and the like. The phenyl-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety includes a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the phenyl moiety, for example, benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4 - phenylbutoxy, 1 ,1-dimethyl-2-phenylethoxy, 5-phenylpentyloxy, 6-phenyl - hexyloxy, 2-methyl-3-phenylpropoxy, 2-(3-methoxyphenyl)ethoxy, 1-(4 - methoxyphenyl)ethoxy, 2-methoxybenzyloxy, 3-(2-ethoxyphenyl)propoxy, 4-(3 - ethoxyphenyl)butoxy, 1 ,1 -dimethyl-2-(4-ethoxyphenyl)ethoxy, 5-(4-isopropoxy - phenyl)pentyloxy, 6-(4-hexyloxyphenyl)hexyloxy, 3,4-dimethoxybenzyloxy, 3,4,5-trimethoxybenzyloxy, 2,5-dimethoxybenzyloxy, 3-methoxybenzyloxy, 4 - methoxybenzyloxy, 2,4-diethoxybenzyloxy, 2,3-dimethoxybenzyloxy, 2,4 - dimethoxybenzyloxy, 2,6-dimethoxybenzyloxy, 2-methylbenzyloxy, 4-ethyl - benzyloxy, 2-(3-methylphenyl)ethoxy, 1-(4-methylphenyl)ethoxy, 3-(2-ethyl - phenyl)propoxy, 4-(3-ethylphenyl)butoxy, 1 ,1-dimethyl-2-(4-ethylphenyl)ethoxy, 5-(4-isopropylphenyl)pentyloxy, 6-(4-hexyphenyl)hexyloxy, 3,4-dimethyl - benzyloxy, 3,4,5-trimethylbenzyloxy, 2,5-dimethylbenzyloxy, 2-methoxy-3 - methylbenzyloxy, and the like.
The 1 ,3-dioxolanyl group having optionally a lower alkyl substituent includes a 1 ,3-dioxolanyl group which may optionally be substituted by 1 to 3 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 1 ,3-dioxolanyl, 2-methyl-1 ,3-dioxolanyl, 4-ethyl-1 ,3 - dioxolanyl, 2-propyl-1 ,3-dioxolanyl, 4-butyl-1 ,3-dioxolanyl, 2-pentyl-1 ,3 - dioxolanyl, 4-hexyl-1 ,3-dioxolanyl, 2,4-dimethyl-1 ,3-dioxolanyl, 2,4,5-trimethyl - 1 ,3-dioxolanyl, and the like.
The lower alkanoyl group includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, t-butylcarbonyl, hexanoyl, and the like.
The morpholino-substituted lower alkoxy group includes a morpholino-substituted alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, morpholinomethoxy, 2-morpholinoethoxy, 1-morpholinoethoxy, 3-(2 - morpholinyl)propoxy, 4-(3-morpholinyl)butoxy, 1 ,1 -dimethyl-2-(2-morpholinyl) - ethoxy, 5-morpholinopentyloxy, 6-morpholinohexyloxy, 2-methyl-3-morpholino - propoxy, and the like. The phenyl-lower alkyl group includes a phenyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzyl, 2-phenylethyl, 1 -phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1 ,1-dimethyl-2 - phenylethyl, 2-methyl-3-phenylpropyl, and the like. The phenyl-lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and may optionally have 1 to 3 straight chain or branched chain alkoxy substituents having 1 to 6 carbon atoms on the phenyl moiety, for example, in addition to the above mentioned phenyl-lower alkyl group, 2-(3 - methoxyphenyl)ethyl, 1-(4-methoxyphenyl)ethyl, 2-methoxbenzyl, 3-methoxy - benzyl, 4-methoxybenzyl, 3-(2-ethoxyphenyl)propyl, 4-(3-ethoxyphenyl)butyl, 1 ,1 -dimethyl-2-(4-ethoxyphenyl)ethyl, 5-(4-isopropoxyphenyl)pentyl, 6-(4-hexyl oxyphenyl)hexyl, 3,4-dimethoxybenzyl, 2,4-dimethoxybenzyl, 3,4,5-trimethoxy - benzyl, and the like.
The furyl-substituted lower alkyl group includes a furyl-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-furyl)methyl, 2-(3-furyl)ethyl, 1-(2-furyl)ethyl, 3-(2-furyl)propyl, 4-(3-furyl)butyl, 5-(2-furyl)pentyl, 6-(3-furyl) - hexyl, 1 ,1-dimethyl-2-(2-furyl)ethyl, 2-methyl-3-(3-furyl)propyl, and the like.
The lower alkoxy-lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethyl, 2-ethoxyethyl, 1-methoxyethyl, 3-methoxypropyl, 4 - ethoxybutyl, 6-propoxyhexyl, 5-isopropoxypentyl, 1 ,1-dimethyl-2-butoxyethyl, 2 methyl-3-tert-butoxypropyl, 2-pentyloxyethyl, hexyloxymethyl, and the like.
The phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl - lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety includes a phenylalkenyl group wherein the alkenyl moiety is a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms and having 1 to 2 double bonds, and the phenyl moiety may opitionally be substituted by 1 to 3 groups selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a halogen atom, an amino group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenylcarbonyl moiety, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a tetrazolyl group having optionally a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (A4 is a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, R40 and R41 are the same or different and each hydrogen atom or a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6 - membered saturated heterocyclic ring with or without being intervened with another nitrogen atom or oxygen atom), a straight chain or branched chain alkylenyloxy group having 2 to 6 carbon atoms, nitro group, and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms having optionally 1 to 3 halogen substituents, for example, styryl, cinnamyl, 4-phenyl-3 butenyl, 4-phenyl-2-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 5 - phenyl-2-pentenyl, 6-phenyl-5-hexenyl, 6-phenyl-4-hexenyl, 6-phenyl-3 - hexenyl, 6-phenyl-2-hexenyl, β-methyl-4-phenyl-3-butenyl, β-methyl-cinnamyl, γ-methyl-cinnamyl, 5-phenyl-2,4-pentadienyl, 4-phenyl-1 ,3-butadienyl, 6 - phenyl-2,4-hexadienyl, 6-phenyl-2,4-hexadienyl, 6-phenyl-3,5-hexadienyl, 6 - phenyl-1,3-hexadienyl, 5-phenyl-1 ,3-pentadienyl, 3-methoxycinnamyl, 4 - methoxycinnamyl, 2-methoxycinnamyl, 4-methoxystyryl, (2-ethoxyphenyl)-2 - butenyl, 5-(3-ethoxyphenyl)-4-pentenyl, α,α-dimethyl-4-ethoxycinnamyl, 5-(4 - isopropoxyphenyl)-2,4-pentadienyl, 6-(4-hexyloxyphenyl)-2-hexenyl, 3,4 - dimethoxycinnamyl, 3,4,5-trimethoxystyryl, 2,5-dimethoxystyryl, 3-methoxy - styryl, 4-methoxystyryl, 2,4-diethoxystyryl, 2,3-dimethoxycinnamyl, 2,4 - dimethoxycinnamyl, 2,6-dimethoxycinnamyl, 2-nitrocinnamyl, 3-nitrocinnamyl, 4-nitrocinnamyl, 4-(2-nitrophenyl)-3-butenyl, 4-(3-nitrophenyl)-2-butenyl, 5-(2 - nitrophenyl)-2-pentenyl, 6-(3-nitrophenyl)-3-hexenyl, 3,4-dinitrocinnamyl, 3,4,5 - trinitrocinnamyl, 2-nitrostyryl, 3-nitrostyryl, 4-nitrostyryl, 3-methylcinnamyl, 2 - methylstyryrl, 4-methylcinnamyl, 2-ethylcinnamyl, 4-isopropylcinnamyl, 4-(3 - ethylphenyl)-3-butenyl, α-methyl-4-isopropylcinnamyl, 5-(4-isopropylphenyl)-2 - pentenyl, 6-(4-hexylphenyl)-2-hexenyl, 3,4-dimethylcinnamyl, 3,4,5-trimethyl - cinnamyl, 2,5-dimethylcinnamyl, 2-chlorocinnamyl, 3-chlorostyryl, 2-fluoro - cinnamyl, 4-chlorocinnamyl, 2-fluorostyryl, 4-(3-fluorophenyl)-2-butenyl, 5-(4 - fluorophenyl)-2-pentenyl, α,α-dimethyl-2-bromocinnamyl, 6-(3-bromophenyl)-2 hexenyl, 4-bromostyryl, 2-iodocinnamyl, 3-iodostyryl, 3,4-dichlorocinnamyl, 3,5 - dichlorocinnamyl, 2,6-dichlorostyryl, 2,3-dichlorocinamyl, 2,4-dichlorostyryl, 3,4 difluorocinnamyl, 3,5-dibromocinnamyl, 3,4,5-trichlorocinnamyl, 2-methoxy-3 - chlorocinnamyl, 3-(4-acetylaminophenyl)-2-butenyl, 3-(2-trifluoromethylphenyl) 2-butenyl, 3-[4-(1-methyltetrazol-5-yl)phenyl]-2-butenyl, 3-(4-cinnamoyiamino - phenyl)-2-butenyl, 3-(3-methoxymethoxyphenyl)-2-butenyl, 3-(2-methoxy - phenyl)-2-butenyl, 3-(3-methoxyphenyl)-2-butenyl, 3-(4-trifluoromethylphenyl) - 2-butenyl, 3-(3-trifluoromethylphenyl)-2-butenyl, 3-(3-acetylaminophenyl)-2 - butenyl, 3-(3-hydroxyphenyl)-2-butenyl, 3-(3-morphoiinocarbonylmethoxy- phenyl)-2-butenyl, 3-(3-diethylaminocarbonylmethoxyphenyl)-2-butenyl, 3-[3-(2 methyl-2-propenyloxy)phenyI]-2-butenyl, 4-chloromethylstyryl, 3-bromomethyl - cinnamyl, 4-(2-iodomethylphenyl)-3-butenyl, 4-[4-(2,2,2-trichloroethyl)phenyl]-2 butenyl, 5-(4-aminophenyl)-4-pentenyl, 5-(3-propionylaminophenyl)-2 - pentenyl, 6-(2-butyrylaminophenyl)-5-hexenyl, 6-(4-pentanoylaminophenyl)-4 - hexenyl, 6-(3-hexanoylaminophenyl)-3-hexenyl, 6-(2,4-diaminophenyl)-2 - hexenyl, 2,4,6-triaminocinnamyl, 4-(3-butenoylamino)styryl, 3-(2-pentenoyl - amino)cinnamyl, 4-[2-(4-hexenoylamino)phenyl]-3-butenyl, 4-[4-(4-ethoxy - butoxy)phenyl]-2-butenyl, 3-[4-(N-acetyl-N-cinnamoylamino)phenyl]-2-butenyl, 5-[2-(6-propoxyhexyloxy)phenyl]-4-pentenyl, 6-[3-(2-pentyloxyethoxy)phenyl]-2 ■ pentenyl, 6-(4-hexyloxymethoxyphenyl)-5-hexenyl, 6-[2-(1 ,1-dimethyl-2-butoxy - ethoxy)phenyl]-3-hexenyl, 3-(2,4-dimethoxymethoxyphenyl)-2-butenyl, 3-(2,4,6 - trimethoxyphenyl)-2-butenyl, 3-[4-(1 -ethyltetrazol-5-yl)phenyl]-2-butenyl, 3-[3-(2 propyltetrazol-5-yl)phenyl]-2-butenyl, 3-[2-(1 -butyltetrazol-5-yl)phenyl]-2 - butenyl, 3-[4-(2-pentyltetrazol-5-yl)phenyl]-2-butenyl, 3-[3-(1-hexyltetrazol-5-yl) - phenyl]-2-butenyI, 2-hydroxycinnamyl, 3-hydroxycinnamyl, 4-hydroxycinnamyl, 4-(2-hydroxyphenyl)-3-butenyl, 5-(2-hydroxyphenyl)-2-pentenyl, 6-(3-hydroxy - phenyI)-3-hexenyl, 2,4-dihydroxycinnamyl, 3,4,5-trihydroxycinnamyl, 4-hydroxy ■ cinnamyl, 4-allyloxystyryl, 3-(2-butenyloxy)cinnamyl, 4-[2-(3-butenyloxy)phenyl] ■ 3-butenyl, 5-[3-(2-pentenyloxy)phenyl]-2-pentenyl, 6-[4-(2-hexenyloxy)phenyl] - 4-hexenyl, 2,4-diallyloxycinnamyl, 2,4,6-triallyloxystyryl, 3-(2-dimethylamino - carbonylethoxyphenyl)-2-butenyl , 4-[4-(3-butylaminocarbonylpropoxy)phenyl] - 3-butenyl, 5-[2-(4-pentylaminocarbonylbutoxy)phenyl]-3-pentenyl, 6-[3-(5-hexyl ■ aminocarbonylpentyloxy)phenyl]-5-hexenyl, 4-[6-(N-methyl-N-propylamino) - carbonylhexyloxyjstyryl, 4-methylaminocarbonylmethoxycinnamyl, 4-(1 - piperidinyl)carbonylmethoxycinnamyl, 3-(1 -piperazinyl)carbonylmethoxystyryl, 4-[3-(1 -pyrrolidinyl)carbonylmethoxyphenyl]-3-butenyl, 3-(2-methoxy-5-chloro - phenyl)-2-butenyl, 3-(2-methoxymethoxy-5-chlorophenyl)-2-butenyl, 3-(2 - hydroxy-5-chlorophenyl)-2-butenyl, and the like. The alkenyl group includes a straight chain or branched chain alkenyl group with 1 to 3 double bonds having 2 to 12 carbon atoms, for example, vinyl, allyl, 3-methyl-2-butenyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2 - pentenyl, 2-hexenyl, 1-heptenyl, 1-octenyl, 1 -nonenyl, 1-decenyl, 1-undecenyl, 2-dodecenyl, 2-heptenyl, 3-heptenyl, 3-methyl-4-heptenyl, 2-methyl-5-heptenyl, 4-methyl-2-heptenyl, 3-methyl-l-heptenyl, 1 ,3-heptadienyl, 1 ,4-heptadienyl, 1,5 heptadienyl, 1 ,6-heptadienyl, 2,4-heptadienyl, 2-methyl-2,4-heptadienyl, 2,6 - dimethyl-2,4-heptadienyl, 2,5-dimethyl-1 ,3-heptadienyl, 2,4,6-trimethyl-2,4 - heptadienyl, 2-octenyl, 3-octenyl, 4-octenyl, 2-methyl-5-octenyl, 3-methyl-6 - octenyl, 2-methyl-7-octenyl, 1,3-octadienyl, 1 ,4-octadienyl, 1 ,5-octadienyl, 1 ,6 - octadienyl, 1 ,7-octadienyl, 2,4-octadienyl, 3,7-octdienyl, 4,8-dimethyi-3,7 - octadienyl, 2,4,6-trimetyl-3,7-octadienyl, 3,4-dimethyl-2,5-octadienyl, 3,7 - dimethyl-2,6-octadienyl, 4,8-dimethyl-2,6-octadienyl, 2-nonenyl, 3-nonenyl, 4 - nonenyl, 2-methyl-5-nonenyl, 2-methyl-6-nonenyl, 2-methyl-7-nonenyl, 2 - methyl-8-nonenyl, 1 ,3-nonadienyl, 1 ,4-nonadienyl, 1,5-nonadienyl, 1 ,6 - nonadienyl, 1 ,7-nonadienyl, 1 ,8-nonadienyl, 2,4-nonadienyl, 3,7-nonadienyl, 4,8-dimethyl-3,7-nonadienyl, 2,4,6-trimethyl-3,7-nonadienyl, 3,4-dimethyl-2,5 - nonadienyl, 4,8-dimethyl-2,6-nonadienyl, 2-decenyl, 3-decenyl, 4-decenyl, 5 - decenyl, 2-methyl-6-decenyl, 3-methyl-7-decenyl, 4-methyl-8-decenyl, 5-methyl 9-decenyl, 1,3-decadienyl, 1 ,4-decadienyl, 1,5-decadienyl, 1 ,6-decadienyl, 1,7 - decadienyl, 1 ,8-decadienyl, 1 ,9-decadienyl, 2-methyl-2,4-decadienyl, 3-methyl - 2,5-decadienyl, 4,8-dimethyl-2,6-decadienyl, 2,4,6-trimethyl-3,7-decadienyl, 2,9-dimethyl-3,7-decadienyl, 2-undecenyl, 3-undecenyl, 4-undecenyl, 5 - undeceyl, 2-methyl-6-undecenyl, 3-methyl-7-undecenyl, 4-methyl-8-undecenyl,
5-methyl-9-undecenyl, 2-methyl-10-undecenyl, 1 ,3-undecadienyl, 1 ,4 - undecadienyl, 1 ,5-undecadienyl, 1 ,6-undecadienyl, 1 ,7-undecadienyl, 1 ,8 - undecadienyl, 1 ,9-undecadienyl, 1 ,10-undecadienyl, 2-methyl-2,4 - undecadienyl, 3-methyl-2,5-undecadienyl, 4,8-dimethyl-2,6-undecadienyl, 2,4,6-trimethyl-3,8-undecadienyl, 2,9-dimethyl-3,8-undecadienyl, 2-dodecenyl, 3-dodecenyl, 4-dodecenyl, 5-dodecenyl, 6-dodecenyl, 2-methyl-7-dodecenyl, 3 methyl-8-dodecenyl, 4-methyl-9-dodecenyl, 5-methyl-10-dodecenyl, 6-methyl - 11-dodecenyl, 2-methyl-2,4-dodecadienyl, 3-methyl-2,5-dodecadienyl, 4,8 - dimethyl-2,6-dodecadienyl, 2,4,6-trimethyl-2,7-dodecadienyl, 2,10-dimethyl-2,8 * dodecadienyl, 2,5-dimethyl-3,7-dodecadienyl, 4,8,12-trimethyl-3,7,11-dodeca - trienyl, 1,3,5-heptatrienyl, 2,4,6-octatrienyl, 1 ,3,6-nonatrienyl, 2,6,8 - dodecatienyl, 1 ,5,7-undecatrienyl, and the like.
The cycloalkyl-lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by a cycloalkyl group having 3 to 8 carbon atoms, for example, cyclohexylmethyl, 2-cyclopropylethyl, 1 -cyclobutylethyl, 3-cyclopentylpropyl, 4-cyclohexylbutyl, 2,2-dimethyl-3-cycloheptylpropyl, 5-cyclooctylpentyl, 6-cyclohexylhexyl, and the like.
The naphthyl-lower alkyl group includes a naphthyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, α-naphthylmethyl, β-naphthylmethyl,
2-(α-naphthyl)ethyl, 1-(β-naphthyl)ethyl, 3-(β-naphthyl)propyl, 4-(α-naphthyl) - butyl, 2-methyl-3-(α-naphthyl)propyl, 5-(β-naphthyl)pentyl, 6-(α-naphthyl)hexyl,
1 ,1-dimethyl-2-(β-naphthyl)ethyl, and the like.
The phenylthio-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenylthio-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and may optionally have 1 to 3 substituents of straight chain or branched chain alkoxy group having 1 to 3 carbon atoms on the phenyl moiety, for example, phenylthiomethyl, 2-phenylthioethyl, 1 - phenylthioethyl, 3-phenylthiopropyl, 4-phenylthiobutyl, 5-phenylthiopentyl, 6 - phenylthiohexyl, 1 ,1-dimethyl-2-phenylthioethyl, 2-methyl-3-phenylthiopropyl, (2-methoxyphenylthio)methyl, (3-methoxyphenylthio)methyl, 2-(4-methoxy - phenylthio)ethyl, 1-(2-ethoxyphenylthio)ethyl, 3-(4-isopropoxyphenylthio) - propyl, 4-(3-pentyloxyphenylthio)butyl, 5-(4-hexyloxyphenylthio)pentyl, 6-(2 - butyloxyphenylthio)hexyl, (3,4-dimethoxyphenylthio)methyl, (3-ethoxy-4 - methoxyphenylthio)methyl, 2-(2,3-dimethoxyphenylthio)ethyl, 1-(2,6-dimethoxy - phenylthio)ethyl, 2-(3,4,5-trimethoxyphenylthio)ethyl, and the like.
The phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenylsulfinylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and may optionally have 1 to 3 substituents of straight chain or branched chain alkoxy group having 1 to 6 carbon atoms on the phenyl moiety, for example, phenylsulfinylmethyl, 2-phenylsulfinylethyl, 1 - phenylsulfinylethyl, 3-phenylsulfinylpropyl, 4-phenylsulfinylbutyl, 5-phenyl - sulfinylpentyl, 6-phenylsulfinylhexyl, 1 ,1 -dimethyl-2-phenylsulfinylethyl, 2 - methyl-3-phenylsulfinylpropyl, (2-methoxyphenylsulfinyl)methyl, (3-methoxy - phenylsulfinyl)methyl, 2-(4-methoxyphenylsulfinyl)ethyl, 1-(2-ethoxyphenyl - suflinyl)ethyl, 3-(4-isoproρoxyphenylsulfinyl)propyl, 4-(3-pentyloxyphenyl - sulfinyl)butyl, 5-(4-hexyoxyphenylsulfinyl)pentyl, 6-(2-butyloxyphenylsulfinyl) - hexyl, (3,4-dimethoxyphenylsulfinyl)methyl, 3-ethoxy-4-methoxyphenylsulfinyl) methyl, 2-(2,3-dimethoxyphenylsulfinyl)ethyl, 1 -(2,6-dimethoxyphenylsulfinyl) - ethyl, 2-(3,4,5-trimethoxyphenylsulfinyl)ethyl, and the like. The phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety includes a phenylsulfonyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents of straight chain or branched chain alkoxy group having 1 to 6 carbon atoms on the phenyl moiety, for example, phenylsulfonyl - methyl, 2-phenylsulfonylethyl, 1-phenylsulfonylethyl, 3-phenylsulfonylpropyl, 4 - phenylsulfonylbutyl, 5-phenylsulfonylpentyl, 6-phenylsulfonylhexyl, 1 ,1 - dimethyl-2-phenylsulfonylethyl, 2-methyl-3-phenylsulfonylpropyl, (2-methoxy - phenylsulfonyl)methyl, (3-methoxyphenylsulfonyl)methyl, 2-(4-methoxyphenyl - sulfonyl)ethyl, 1 -(2-ethoxyphenylsulfonyl)ethyl, 3-(4-isopropoxyphenylsulfonyl) ■ propyl, 4-(3-pentyloxyphenylsulfonyl)butyl, 5-(4-hexyloxyρhenylsulfonyl)pentyl, 6-(2-butyloxyphenylsulfonyl)hexyl, 3,4-dimethoxyphenylsulfonylmethyl, 3 - ethoxy-4-methoxyphenylsulfonyl)methyl, 2-(2,3-dimethoxyphenylsulfonyl)ethyl, 1-(2,6-dimethoxyphenylsulfonyl)ethyl, 2-(3,4,5-trimethoxyphenylsulfonyl)ethyl, and the like.
The 5- to 14-membered saturated or unsaturated hetero - monocyclic, heterobicyclic or heterotricyclic group having 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, thienyl, quinolyl, 1 ,4-dihydroquinolyl, benzothiazolyl, pyrazinyl, pyrimidyl, pyridazinyl, pyrrolyl, carbostyril, 3,4-dihydrocarbostyril, 1 ,2,3,4-tetrahydroquinolyl, indolyl, isoindolyl, indolinyl, benzimidazolyl, benzoxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, quinoxalinyl, cinnonyl, phthalazinyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, 2,3-dihydrobenzofuryl, perhydrobenzofuryl, benzofuryl, benzothienyl, 4H-chromenyl, 1 ,3,4 - oxadiazolyl, 1 ,2,4-triazolyl, 1 ,2,3,4-tetrazolyl, 1 ,3,4-triazolyl, 1 ,2,4-oxadiazolyl, 2,3-dihydrobenzofuryl, perhydrobenzofuryl, 5-1 H-indazolyl, furyl, pyrrolinyl, nolyl, oxazolyl, isoxazolyl, thiazolyl, thiazolidinyl, 1 ,2,3,5-oxathiadiazolyl, isothiazolyl, pyranyl, pyrazolidinyl, quinuclidinyl, 1 ,4-benzoxazinyl, 3,4-dihydro - 2H-1 ,4-benzoxazinyl, 1 ,4-benzothiazinyl, 1 ,2,3,4-tetrahydroquinoxalinyl, 1 ,3 - dithia-2,4-dihydronaphthalenyl, 1 ,4-dithianaphthalenyl, furo[3,2-c]pyridyl, furo[2,3-g]quinolyl, 3,4-dihydrofuro[2,3-g]quinolyl, 1 ,2,3,4-tetrahydrofuro[2,3 - gjquinolyl, 1 ,4-benzodioxanyl, 1 ,2,4-triazinyl, naphtho[2,1-b]furyl, imidazo[1 ,2 - ajpyridyl, and the like.
The lower alkyl group which is substituted by a 5- to 14 - membered saturated or unsaturated heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom includes, for example, pyrrolidinylmethy, 2 - piperidinylethyl, 3-piperazinylpropyl, 4-morpholinobutyl, (2-pyridyl)methyl, (3 - pyridyl)methyl, (2-thienyl)methyl, (3-quinolyl)methyl, 5-(6-quinolyl)pentyl, 6-(1 ,4 dihydro-2-quinolyl)hexyl, (2-benzothiazolyl)methyl, 2-(3-pyrazinyl)ethyl, 1-(2 - pyrimidyl)ethyl, 3-(3-pyridazinyl)propyl, 4-(2-pyrrolyl)butyl, 5-(3-carbostyril) - pentyl, 6-(3,4-dihydrocarbostyril-6-yl)hexyl, (1 ,2,3,4-tetrahydroquinolyl-8 - yl)methyl, (2-indolyl)methyl, (3-indolyl)methyl, 2-(3-indolyl)ethyl, (4-isoindolyl) - methyl, 2-(3-indolinyl)ethyl, (2-benzoimidazolyl)methyl, 3-(5-benzoxazolyl) - propyl, 4-(4-imidazolidinyl)butyl, 5-(1 -isoquinolyl)pentyl, 6-(7-quinazolidinyl) - hexyl, (8-quinoxalinyl)methyl, 1 -(4-cinnolinyl)ethyl, 3-(5-phthalazinyl)propyl, 4 - (6-chromanyl)butyl, 5-(4-isoindolinyl)pentyl, 6-(7-isochromanyl)hexyl, (3 - pyrazolyl)methyl, 2-(2-imidzolyl)ethyl, 3-(3-pyrazolidinyl)propyl, (2-benzofuryl) - methyl, (3-benzofuryl)methyl, 4-(6-benzofuryl)butyl, (2-benzothienyl)methyl, (3 - benzothienyl)methyl, 5-(5-benzothienyl)pentyl, [6-(4H-chromenyl)]methyl, (2,3 - dihydro-2-benzofuryl)methyl, (2-perhydrobenzofuryl)methyl, (5-1 H-indazolinyl) - methyl, thienylmethyl, 1-(5-isoindolinyl)ethyl, 3-(2-imidazolinyl)propyl, 4-(2 - pyrrolinyl)butyl, (2-furyl)methyl, (4-oxazolyl)methyl, (5-oxazolyl)methyl, 5-(4 - oxazolyOpentyl, 6-(3-isoxazolyl)hexyl, (4-thiazolyl)methyl, (2-thiazolyl)methyl, 2 ■ (3-isothiazolyl)ethyl, (2-pyranyl)methyl, 3-(3-pyrazolidinyl)propyl, 4-(2- pyrazolinyl)butyl, 5-(2-quinuclidinyl)pentyl, (1 ,4-benzoxazin-6-yl)methyl, (3,4 - dihydro-2H-1 ,4-benzoxazin-2-yl)methyl, (1 ,4-benzothiazin-5-yl)methyl, (1 ,2,3,4 tetrahydroquinoxalinyl-6-yl)methyl, (1 ,3-dithia-2,4-dihydronaphthalen-6-yl) - methyl, (1 ,4-dithianaphthalen-7-yl)methyl, (5-thiazolyl)methyl, (1 ,3,4 - oxadiazolin-5-yl)methyl, (1,2,4-triazol-5-yl)methyl, (1,2,3,4-tetrazol-5-yl)methyl,
(I.S^-triazol-δ-y methyl, (1 ,2,4-oxadiazol-5-yl)methyl, (1 ,2,4-triazin-3-yl) - methyl, (thiazolidin-5-yl)methyl, (1 ,2,3,5-oxathiazolin-4-yl)methyl, (3-furyl) - methyl, (2-furyl)methyl, (2-imidazolyl)methyl, 2-(5-thiazolyl)ethyl, 1 -(1 ,3,4 - oxadiazolin-2-yl)ethyl, 3-(1 ,2,4-thazol-3-yl)propyl, 4-(1 ,2,3,4-tetrazol-5-yl)butyl, 6-(1 ,3,4-triazol-2-yl)hexyl, 2-(1 ,2,4-oxadiazol-3-yl)ethyl, 1 -(1 ,2,4-triazin-5-yl) - ethyl, 3-(thiazolidin-2-yl)propyl, 4-(1 ,2,3,5-oxathiadiazolin-4-yl)butyl, 5-(furo[3,2 c]pyridin-2-yl)pentyl, 6-(furo[2,3-g]quinolin-7-yl)hexyl, (3,4-dihydrofuro[2,3-g] - quinolin-8-yl)methyl, 2-(1 ,2,3,4-tetrahydrofuro[2.3-g]quinolin-4-yl)ethyl, (1 ,4 - benzodioxan-2-yl)methyl, 1-(1,4-benzodioxadin-3-yl)ethyl, (2,3-dihydrobenzo - furan-2-yl)methyl, (perhydrobenzofuran-2-yl)methyl, naphtho[2,1-b]furylmethyl, 4-(naphtho[2,1-b]furyl)pentyl, imidazo[1,2-a]pyridylmethyl, 2-(imidazo[1 ,2-a] - pyridyl)ethyl, 1-(imidazo[1,2-a]pyridyl)ethyl, and the like.
The phenoxy-substituted lower alkyl group includes a phenoxyalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, phenoxymethyl, 2 - phenoxyethyl, 1-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 5-phenoxy - pentyl, 6-phenoxyhexyl, 1 ,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxy - propyl, and the like.
The phenyl-lower alkoxy group which may optionally have an amino substituent having optionally a lower alkanoyl substituent on the phenyl moiety includes a phenylalkoxy group, wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents of amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4 - phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1 ,1-dimethyl-2-phenyl - ethoxy, 2-methyl-3-phenylpropoxy, 4-acetylaminobenzyloxy, 2-(2-propionyl - aminophenyl)ethoxy, 1 -(3-butyrylaminophenyl)ethoxy, 3-(4-pentanoylamino- phenyl)propoxy, 4-(3-tert-butylcarbonylaminophenyl)butoxy, 5-(4-hexanoyl - aminophenyl)pentyloxy, 6-(3,4-bisacetylaminophenyl)hexyloxy, 3,4,5-triacetyl - aminobenzyloxy, 2,4-bisacetylaminobenzyloxy, 4-aminobenzyloxy, 2,3 - diaminobenzyloxy, 2,4,6-triaminobenzyloxy, 2-(3-aminophenyl)ethoxy, 3-(2 - aminophenyl)propoxy, and the like.
The lower alkoxy-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethoxy, 3-methoxypropoxy, 4 - ethoxybutoxy, 6-propoxyhexyloxy, 5-isopropoxypentyloxy, 1 ,1 -dimethyl-2 - butoxyethoxy, 2-methyl-3-tert-butoxypropoxy, 2-pentyloxyethoxy, hexyloxy - methoxy, and the like.
The lower alkanoyloxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyloxymethyl, 2,2-dimethylpropionyloxy - methyl, propionyloxymethyl, 2-propionyloxyethyl, 1 -acetyloxyethyl, 1-butyryl - oxyethyl, 3-acetyloxypropyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-tert - butylcarbonyloxyhexyl, 1 ,1 -dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxy - propyl, and the like.
The halogen-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethyl, trichloro - methyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3 - chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloro - pentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, 5-bromo - hexyl, 5,6-dichlorohexyl, and the like.
The tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring includes a tetrazolyl group having optionally a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the tetrazole ring, for example, tetrazolyl, 1-methyltetrazolyl, 2-methyltetrazolyl, 5-ethyltetrazolyl, 5 propyltetrazolyl, 1-butyltetrazolyl, 2-pentyltetrazolyl, 1 -hexyltetrazolyl, and the like.
The phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy-substituted lower alkoxy group, hydroxy group, a halogen atom and a lower alkoxy group includes a phenyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, hydroxy group, a halogen atom and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3 - methylphenyl, 4-methylphenyl, 2-ethyl phenyl, 3-ethylphenyl, 4-ethylphenyl, 3 - isopropylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 2,5-dimethylphenyl, 3,4,5 - trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2 - ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-pentyl - oxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3 - ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5 - dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxy - phenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chloro - phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3 - bromophenyl, 4-bromophenyI, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 3,4 - dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2,3-dichlorophenyl, 2,4 • dichlorophenyl, 3,4-difluorophenyl, 3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2 - methoxy-5-chlorophenyl, 3-chloro-4-methoxyphenyl, 3-methoxy-5-iodophenyl, 3,4-dimethoxy-5-bromophenyl, 3,5-diiodo-4-methoxyphenyl, 2-hydroxy-5 - chlorophenyl, 2-methoxymethoxy-5-chlorophenyl, 2-hydroxyphenyl, 3-hydroxy - phenyl, 4-hydroxyphenyl, 2,3-dihydroxyphenyl, 3,4-dihydroxyphenyl, 3,4,5 - trihydroxyphenyl, 2-methoxymethoxyphenyl, 3-(3-methoxypropoxy)phenyl, 4-(4 - ethoxybutoxy)phenyl, 2-(6-propoxyhexyloxy)phenyl, 3-(5-isopropoxypentyloxy) - phenyl, 4-(1 ,1-dimethyl-2-butoxyethoxy)phenyl, 2-(2-methyl-3-tert-butoxy - propoxy)phenyl, 3-(2-pentyloxyethoxy)phenyl, 4-hexyloxymethoxyphenyl, 2,3 - dimethoxymethoxyphenyl, 3,4,5-trimethoxymethoxyphenyl, and the like.
The lower alkenyl group includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, vinyl, allyl, 2- butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl, 2-hexenyl, and the like. The morpholinocarbonyl-lower alkoxy group includes a morpholinocarbonylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxyl group having 1 to 6 carbon atoms, for example, morpholinocarbonylmethoxy, 2-morpholinocarbonylethoxy, 1-morpholino - carbonylethoxy, 3-(2-morpholinocarbonyl)propoxy, 4-(3-morpholinocarbonyl) - butoxy, 1 ,1-dimethyl-2-(2-morpholinylcarbonyl)ethoxy, 5-morpholinylcarbonyl - pentyloxy, 6-morpholinocarbonylhexyloxy, 2-methyl-3-morpholinocarbonyl - propoxy, and the like. The morpholinocarbonyl-lower alkyl group includes a morpholinocarbonylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, morpholinocarbonylmethyl, 2-morpholinocarbonylethyl, 1 -morpholinocarbonyl - ethyl, 3-(2-morpholinocarbonyl)propyl, 4-(3-morpholinocarbonyl)butyl, 1 ,1 - dimethyl-2-(2-morpholinocarbonyl)ethyl, 5-morpholinocarbonylpentyl, 6 - morpholinocarbonylhexyl, 2-methyl-3-morpholinocarbonylpropyl, and the like.
The cycloalkylcarbonyl group includes a cycloalkylcarbonyl group having 3 to 8 carbon atoms in the cycloalkyl moiety, for example, cyclopropyl - carbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, and the like.
The phenyl-lower alkenylcarbonyl group includes a phenylalkenyl carbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenylcarbonyl moiety, for example, cinnamoyi, 4-phenyl-2-butenoyl, 4-phenyl • 3-butenoyl, 5-phenyl-4-pentenoyl, 5-phenyl-3-pentenoyl, 5-phenyl-2 - pentenoyi, 6-phenyl-5-hexenoyl, 6-phenyl-4-hexenoyl, 6-phenyl-3-hexenoyl, 6 - phenyl-2-hexenoyl, 2-methyl-4-phenyl-3-butenoyl, 2-methyl-cinnamoyl, 1 - methyl-cinnamoyl, and the like.
The 5- to 6-membered saturated heterocyclic group which is formed by combining R6 and R7, R9 and R10, R40 and R41 or R52 and R53 together with the adjacent nitrogen atom with or without being intervening with nitrogen atom or oxygen atom, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, and the like. The above heterocyclic group having 1 to 3 substituents selected from hydroxy group, a lower alkyl group and a phenyl-lower alkyl group includes the above mentioned heterocyclic groups having 1 to 3 sustituents selected from hydroxy group, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 3-hydroxypyrrolidinyl, 2-hydroxypyrrolidinyl, 4-hydroxypiperidinyl, 3-hydroxypiperidinyl, 2-hydropiperidinyl, 3-hydroxypiperazinyl, 2-hydroxy - piperazinyl, 3-hydroxymorpholino, 2-hydroxymorpholino, 4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(3-phenylpropyl)pyrrolidinyl, 4-(4-phenylbutyl) - piperidinyl, 3-(5-phenylpentyl)morpholino, 2-(6-phenylhexyl)piperazinyl, 4 - methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propyl - pyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 2 ■ hexylpiperazinyl, 3-methyl-4-benzylpiperazinyl, 3-ethyl-4-hydroxypiperidinyl, 3 - methyl-4-benzylpyrrolidinyl, and the like.
The amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group includes an amino group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenylcarbonyl moiety, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, t-butyl - carbonylamino, hexanoylamino, cinnamoylamino, 4-phenyl-3-butenoylamino, 4-phenyl-2-butenoylamino, 5-phenyl-4-pentenoylamino, 5-phenyl-3-pentenoyl - amino, 5-phenyl-2-pentenoylamino, 6-phenyl-5-hexenoylamino, 6-phenyl-4 - hexenoylamino, 6-phenyl-3-hexenoylamino, 6-phenyl-2-hexenoylamino, 2 - methyl-4-phenyl-3-butenoylamino, 2-methyl-cinnamoylamino, 1 -methyl - cinnamoylamino, N-acetyl-N-cinnamoylamino, and the like. The amino group having optionally a lower alkanoyl substituent includes an amino group having optionally a substituent of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetyamino, propionylamino, butyrylamino, isobutyryl- amino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like. The alkylsufinyl group includes a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, butylsulfinyl, tert-butylsuifinyl, pentylsulfinyl, hexylsulfinyl, and the like.
The lower alkylthio group includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like. The lower alkylsulfonyl group includes a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl, butysulfonyl, tert-butysulfonyl, pentylsulfonyl, hexylsulfonyl, and the like.
The lower alkanoyloxy group includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert - butylcarbonyloxy, hexanoyloxy, and the like.
The amino-substituted lower alkyl group having optionally a substituent selected from a lower alkylsulfonyl group and a lower alkanoyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 groups selected from a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1 - aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1 ,1 - dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, formylaminomethyl, 1-acetyl - aminoethyl, 2-propionylaminoethyl, 3-butyrylaminopropyl, 4-pentanoylamino - pentyl, 5-hexanoylaminohexyl, 6-isobutyrylaminohexyl, 1 ,1-dimethyl-2-acetyl - aminoethyl, 2-methyl-3-formylaminopropyl, methylsulfonylaminomethyl, 2 - ethylsulfonylaminoethyl, 1 -isopropylsulfonylaminoethyl, 3-butylsulfonylamino - propyl, 4-tert-butylsulfonylaminobutyl, 5-pentylsulfonylaminopentyl, 6-hexyl - sulfonylaminohexyl, 1 ,1-dimethyl-2-methylsulfonylaminoethyl, 2-methyl-3 - ethylsulfonylaminopropyl, N-methylsulfonylamino-N-acetylaminomethyl, and the like.
The 1 ,3-dioxolanyl-substituted lower alkyl group having optionally a lower alkyl substituent includes a 1 ,3-dioxolanyl-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (1 ,3-dioxolan-2-yl)methyl, 2-(1 ,3-dioxolan-4-yl)ethyl, 1-(1 ,3-dioxolan - 2-yl)ethyl, 3-(1 ,3-dioxolan-4-yl)propyl, 4-(1 ,3-dioxolan-2-yl)butyl, 2-(1 ,3 - dioxolan-2-yl)propyl, 5-(1 ,3-dioxolan-2-yl)pentyl, (4-hexyl-1 ,3-dioxolan-2-yl) - methyl, (2,4-dimethyl-1 ,3-dioxolan-2-yl)methyl, 6-(1 ,3-dioxolan-3-yl)hexyl, 4-(2 - propyl-1 ,3-dioxolan-2-yl)butyl, 5-(4-butyl-1 ,3-dioxolan-2-yl)pentyl, 6-(2-pentyl - 1 ,3-dioxolan-2-yl)hexyl, 1 ,1-dimethyl-2-(1 ,3-dioxolan-2-yl)ethyl, 2-methyl-3-(1 ,3 dioxolan-2-yl)propyl, (2-methyl-1 ,3-dioxolan-2-yl)methyl, 2-(4-ethyl-1 ,3 - dioxolan-2-yl)ethyl, 3-(2,4,5-trimethyl-1 ,3-dioxolan-2-yl)propyl, and the like. The alkanoyl-substituted lower alkyl group includes an alkanoylalkyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, formylmethyl, acetylmethyl, 2-propionylethyl, 1-butyrylethyl, 3 - isobutyrylpropyl, 4-pentanoylbutyl, 5-hexanoylhexyl, 6-tert-butylcarbonylhexyl,
1 ,1-dimethyl-2-acetylethyl, 2-methyl-3-acetylmethyl, and the like.
The aminocarbonyl-substituted lower alkyl group which may optionally have a lower alkyl substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an aminocarbonyl having optionally 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonylmethyl, 2-aminocarbonylethyl, 1-aminocarbonylethyl, 3 - aminocarbonylpropyl, 4-aminocarbonylbutyl, 5-aminocarbonylpentyl, 6 - aminocarbonylhexyl, 1 ,1 -dimethyl-2-aminocarbonylethyl, 2-methyl-3-amino - carbonylpropyl, methylaminocarbonylmethyl, 1 -ethylaminocarbonylethyl, 2 - propylaminocarbonylethyl, 3-isopropylaminocarbonylpropyl, 4-butylamino - carbonylbutyl, 5-pentylaminocarbonylpentyl, 6-hexyl ;minocarbonylhexyl, dimethylaminocarbonylmethyl, 2-diethylaminocarbonylethyl, 2-dimethylamino- carbonylethyl, (N-ethyl-N-propylamino)carbonylmethyl, 2-(N-methyl-N-hexyl - amino)carbonylethyl, and the like.
The lower alkoxycarbonyl-substituted lower alkenyl group includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy - carbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, 2 ■ methoxycarbonylvinyl, 2-ethoxycarbony vinyl, 3-propoxycarbonylallyl, 4-butoxy - carbonyl-2-butenyl, 4-pentyloxycarbonyl-3-butenyl, 3-hexyloxycarbonyl-1 - methylallyl, 5-isopropoxycarbonyl-2-pentenyl, 6-tert-butoxycarbonyl-2-hexenyl, and the like.
The aminocarbonyl-substituted lower alkenyl group which may optionally have a lower alkyl substituent includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms which is substitued by an aminocarbonyl group having optinally have 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 2 aminocarbonylvinyl, 3-aminocarbonylallyl, 4-aminocarbonyl-2-butenyl, 4 - aminocarbonyl-3-butenyl, 3-aminocarbonyl-1 -methylallyl, 5-aminocarbonyl-2 - pentenyl, 6-aminocarbonyl-2-hexenyl, 2-methylaminocarbonylvinyl, 3-ethyl - aminocarbonylallyl, 4-propylaminocarbonyl-2-butenyl, 4-isopropylamino - carbonyl-3-butenyl, 3-butylaminocarbonyl-1 -methylallyl, 5-pentylamino - carbonyl-2-pentenyl, 6-hexylaminocarbonyl-2-hexenyl, 2-dimethylamino - carbonylvinyl, 2-diethylaminocarbonylvinyl, 3-(N-ethyl-N-propylaminocarbonyl) allyl, 4-(N-methyl-N-hexylaminocarbonyl)-2-butenyl, and the like.
The carboxy-substituted lower alkenyl group includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, 2-carboxyvinyl, 3-carboxyallyl, 4-carboxy-2-butenyl, 4-carboxy-3 - butenyl, 3-carboxy-1 -methylallyl, 5-carboxy-2-pentenyl, 6-carboxy-2-hexenyl, and the like.
The aminocarbonyl group having optionally a lower alkyl substituent includes an aminocarbonyl group which may optionally have 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethyl - aminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butyl- aminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexyl - aminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropyl - aminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexyl - aminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylamino - carbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, and the like.
The phenylsulfonyl group having optionally a lower alkyl substituent includes a phenylsulfonyl group having optionally 1 to 3 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, phenylsulfonyl, 2-methyl phenylsulfonyl, 3 - methylphenylsulfonyl, 4-methylphenylsulfonyl, 2-ethylphenylsulfonyl, 3 - ethylphenylsulfonyl, 4-ethylphenylsulfonyl, 3-isopropylphenylsulfonyl, 4 - hexylphenylsulfonyl, 3,4-dimethylphenylsulfonyl, 2,5-dimethylphenylsulfonyl, 3,4,5-trimethylphenylsulfonyl, and the like. The phenyl-lower alkenyl group includes a phenylalkenyl group wherein the alkenyl moiety is a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, styryl, cinnamyl, 4-phenyl-3-butenyl, 4 phenyl-2-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 5-phenyl-2 - pentenyl, 6-phenyl-5-hexenyl, 6-phenyl-4-hexenyl, 6-phenyl-3-hexenyl, 6 - phenyl-2-hexenyl, 2-methyl-4-phenyl-3-butenyl, 2-methyl-cinnamyl, 1 -methyl - cinnamyl, and the like.
The benzoyi group which may optionally have 1 to 3 substituents selected from a lower alkoxy group, a halogen atom, an amino group having optionally a lower alkanoyl substituent, and hydroxy group on the phenyl moiety includes a benzoyi group which may optinally have 1 to 3 substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a halogen atom, an amino group having optionally a straight chain or branched chain alkanoyl substituent having 1 to 6 carbon atoms and hydroxy group on the phenyl moiety, for example, benzoyi, 2-chlorobenzoyl, 3 - chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl, 3-fluorobenzoyl, 4-fluoro - benzoyi, 2-bromobenzoyl, 3-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 4 - iodobenzoyl, 3,5-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,4-dichlorobenzoyl, 3,4-difluorobenzoyl, 3,5-dibromobenzoyl, 3,4,5-trichlorobenzoyl, 2-methoxy- benzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxy - benzoyi, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 4-hexyloxybenzoyl, 3,4 - dimethoxybenzoyl, 3,4-diethoxybenzoyl, 3,4,5-trimethoxybenzoyl, 2,5 - dimethoxybenzoyl, 3-methoxy-4-chlorobenzoyl, 2-chloro-6-methoxybenzoyl, 2 - methoxy-5-chlorobenzoyl, 2-aminobenzoyl, 3-aminobenzoyl, 4-aminobenzoyl,
2-hydroxybenzoyl, 3-hydroxybenzoyl, 4-hydroxybenzoyl, 2,5-diaminobenzoyl, 3,4,5-triaminobenzoyl, 2-formylaminobenzoyl, 3-acetyaminobenzoyl, 4-acetyl - aminobenzoyl, 2-acetylaminobenzoyl, 3-propionylaminobenzoyl, 4-butyryl - aminobenzoyl, 2-isobutyrylaminobenzoyl, 3-pentanoylaminobenzoyl, 3-tert - butylcarbonylaminobenzoyl, 4-hexanoylaminobenzoyl, 2,6-diacetylamino - benzoyi, 2,4-dihydroxybenzoyl, 2,4,6-thhydroxybenzoyl, 2-hydroxy-5-chloro - benzoyi, and the like.
The amino-substituted lower alkanoyl group having optionally a lower alkanoyl substituent includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substitued by an amino group having optionally 1 to 2 substituents of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, 2-aminoacetyl, 3 - aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6 - aminohexanoyl, 2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl, 2 - acetylaminoacetyl, 2-acetylaminopropionyl, 3-propionylaminopropionyl, 3 - isopropionylaminopropionyl, 4-butyrylaminobutyryl, 5-pentanoylamino - pentanoyl, 6-hexanoylaminohexanoyl, 2-formylaminoacetyl, and the like.
The amino-substituted sulfonyl group having optionally a lower alkyl substituent includes an aminosulfonyl group which may optionally have 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminosulfonyl, methylaminosulfonyl, ethylamino - sulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, butylaminosulfonyl, tert - butylaminosulfonyl, pentylaminosulfonyl, hexylaminosulfonyl, dimethylamino - sulfonyl, diethylaminosulfonyl, dipropylaminosulfonyl, dibutylaminosulfonyl, dibutylaminosulfonyl, dipentylaminosulfonyl, dihexylaminosulfonyl, N-methyl-N - ethylaminosulfonyl, N-ethyl-N-propylaminosulfonyl, N-methyl-N-butylamino - sulfonyl, N-methyl-N-hexylaminosulfonyl, and the like.
The lower alkeneldioxy group includes a straight chain or branched chain alkylenedioxy group having 1 to 4 carbon atoms, for example, methylenedioxy, ethylenedioxy, trimethylenedioxy, tetramethylenendioxy, and the like.
The phenyl group having optionlly a lower alkoxy substituent includes a phenyl group which may optionally have 1 to 3 substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2 - ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-pentyl - oxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3-ethoxy-4-methoxy - phenyl, 2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5 - dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxy - phenyl, 3,4,5-trimethoxyphenyl, and the like.
The 2,3-dihydro-1 H-indenyl-substituted lower alkyl group which may optionall have a substituent selected from oxo group, hydroxy group and silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1H-indenyl ring includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a 2,3-dihydro-1 H-indenyl group having optionally 1 to 3 substituents selected from oxo group, hydroxy group and a silyloxy group having 3 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2,3-dihydro-1 H-inden-2-yl) - methyl, 2-(2,3-dihydro-1 H-inden-1 -yl)ethyl, 1 -(2,3-dihydro-1 H-inden-3-yl)ethyl, 3-(2,3-dihydro-1 H-inden-4-yl)propyl, 4-(2,3-dihydro-1 H-inden-5-yl)butyl, 5-(2,3 ■ dihydro-1 H-inden-6-yl)pentyl, 6-(2,3-dihydro-1 H-inden-7-yl)hexyl, (1 -oxo-2,3 - dihydro-1 H-inden-2-yl)methyl, (1-hydroxy-2,3-dihydro-1 H-inden-2-yl)methyl, (1 dimethyl,tert-butylsilyloxy-2,3-dihydro-1 H-inden-2-yl)methyl, (1 ,3-dihydroxy-2,3 dihydro-1 H-inden-2-yl)methyl, [1 ,3-bis(thmethylsilyloxy)-2,3-dihydro-1 H-inden - 2-yl)methyl, (1 ,3,7-trihydroxy-2,3-dihydro-1 H-inden-2-yl)methyl, [1 ,3,4-tri - (dimethyl, ethylsilyloxy)-2,3-dihydro-1H-inden-2-yl)methyl, and the like.
The silyloxy group having a lower alkyl substituent includes a silyloxy group being substituted by three straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, trimethylsilyloxy, triethyl - silyloxy, triisopropylsilyloxy, tributylsilyloxy, tri-tert-butylsilyloxy, tripentylsilyloxy, trihexylsilyloxy, dimethyl, tert-butylsilyloxy, and the like. The phenyl group having optionally a substituent selected from a lower alkoxy group and a halogen atom on the phenyl ring includes a phenyl group which may optionaly be substituted by 1 to 3 groups selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a halogen atom, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4 - methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4 - isopropoxyphenyl, 4-pentyloxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4 - diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxy - phenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3 - chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2 bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4 - iodophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2,3 - dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluorocphenyl, 3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2-methoxy-5-chlorophenyl, 3-chloro-4-methoxyphenyl, 3 - methoxy-5-iodophenyl, 3,4-dimethoxy-5-bromophenyl, 3,5-iodo-4-methoxy - phenyl, and the like.
The saturated or unsaturated 5- to 6-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, thienyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, imidazolidinyl, pyrazolyl, imidazolyl, pyrazolidinyl, 1 ,3,4-oxadiazolyl, 1 ,2,4 - triazolyl, 1 ,2,3,4-tetrazolyl, 1 ,3,4-triazolyl, 1 ,2,4-oxadiazolyl, furyl, pyrrolinyl, oxazolyl, isoxazolyl, thiazolyl, thiazolidinyl, 1 ,2,3,5-oxathiadiazolyl, isothiazolyl, pyranyl, pyrazolidinyl, 1 ,2,4-triazinyl, and the like.
The lower alkyl group substitued by a 5- to 6-membered saturated or unsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by the above mentioned heterocyclic group, for example, pyrrolidinylmethyl, 2 - piperidinylethyl, 3-piperazinylpropyl, 4-morpholinobutyl, (2-pyridyl)methyl, (3 - pyridyl)methyl, (2-thienyl)methyl, 2-(3-pyrazinyl)ethyl, 1-(2-pyrimidyl)ethyl, 3-(3 - pyridazinyl)propyl, 4-(2-pyrrolyl)butyl, 4-(4-imidazolidinyl)butyl, (2-imidazolyl)- methyl, (3-pyrazolyl)methyl, 2-(2-imidazolyl)ethyl, 3-(3-pyrazolidinyl)propyl, thienylmethyl, 3-(2-imidazolinyl)propyl, 4-(2-pyrrolinyl)butyl, (2-furyl)methyl, (4 - oxazolyl)methyl, (5-oxazolyl)methyl, 5-(4-oxazolyl)pentyl, 6-(3-isooxazolyl) - hexyl, (4-thiazolyl)methyl, (2-thiazolyl)methyl, 2-(3-isothiazolyl)ethyl, (2-pyranyl) methyl, 3-(3-pyrazolidinyl)propyl, 4-(2-pyrazolinyl)butyl, (5-thiazolyl)methyl,
(1,3,4-oxadiazolin-5-yl)methyl, (1 ,2,4-triazol-5-yl)methyl, (1 ,2,3,4-tetrazol-5-yl) - methyl, (1 ,3,4-triazol-5-yl)methyl, (1 ,2,4-oxadiazol-5-yl)methyl, (1 ,2,4-triazin-3 - yl)methyl, (thiazolidin-5-yl)methyl, (1 ,2,3,5-oxathiadiazolin-4-yl)methyl, (2-furyl) - methyl, (3-furyl)methyl, 2-(5-thiazolyl)ethyl, 1-(1 ,3,4-oxadiazolin-2-yl)ethyl, 3 - (1 ,2,4-thazol-3-yl)propyl, 4-(1 ,2,3,4-tetrazol-5-yl)butyl, 6-(1 ,3,4-triazol-2-yl) - hexyl, 2-(1 ,2,4-oxadiazol-3-yl)ethyl, 1-(1 ,2,4-triazin-5-yl)ethyl, 3-(thiazolidin-2 - yl)propyl, 4-(1 ,2,3,5-oxathiadiazolin-4-yl)butyl, and the like.
The lower alkenyl group substituted by a 5- to 14-membered saturated or unsaturated heteromonocylic, heterobicyclic or heterothcyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom includes the above mentioned heterocyclic group-substituted alkenyl group wherein the alkenyl moiety is a straight chain or branched chain alkenyl group with 1 to 2 double bounds having 2 to 6 carbon atoms, for example, 2-benzofurylvinyl, 3-benzofuryl-2-propenyl, 4-benzofuryl-3-butenyl, 3 - benzofuryl-2-butenyl, 2-methyl-3-benzofuryl-2-propenyl, 5-benzofuryl-4 - petenyl, 5-benzofuryl-2-pentenyl, 4-benzofuryl-3-pentenyl, 6-benzofuryl-5 - hexenyl, 6-benzofuryl-4-hexenyl, 6-benzofuryl-3-hexenyl, 6-benzofuryl-2 - hexenyl, β-methyl-4-benzofuryl-3-butenyl, 5-benzofuryl-2,4-pentadienyl, 4 - benzofuryl-1,3-butadienyl, 6-benzofuryl-2,4-hexadienyl, 6-benzofuryl-3,5 - hexadienyl, 6-benzofuryl-1 ,3-hexadienyl, 5-benzofuryl-1 ,3-pentadienyl, 2 - benzothienylvinyl, 3-benzothienyl-2-propenyl, 4-benzothienyl-3-butenyl, 3 - benzothienyl-2-butenyl, 2-methyl-3-benzothienyl-2-propenyl, 5-benzothienyl-4 - petenyl, 5-benzothienyl-2-pentenyl, 6-benzothienyl-5-hexenyl, 6-benzothienyl -
4-hexenyl, 6-benzothienyl-3-hexenyl, 6-benzothienyl-2-hexenyl, β-methyl-4 - benzothienyl-3-butenyl, 5-benzothienyl-2,4-pentadienyl, 4-benzothienyl-1 ,3 - butadienyl, 6-benzothienyl-2,4-hexadienyl, 6-benzothienyl-3,5-hexadienyl, 6- benzothienyl-1 ,3-hexadienyl, 5-benzothienyl-1 ,3-pentadienyl, 2-(furo[3,2-c]- pyridyl)vinyl, 3-(furo[3,2-c]pyridyl)-2-propenyl, 4-(furo[3,2-c]pyridyl)-3-butenyl, 3 (furo[3,2-c]pyridyl)-2-butenyl, 2-methyl-3-(furo[3,2-c]pyridyl)-2-propenyl, 5 - (furo[3,2-c]pyridyl)-4-petenyl, 5-(furo[3,2-c]pyhdyl)-2-pentenyl, 6-(furo[3,2 - c]pyridyl)-5-hexenyl, 6-(furo[3,2-c]pyridyl)-4-hexenyl, 6-(furo[3,2-c]pyridyl)-3 - hexenyl, 6-(furo[3,2-c]pyridyl)-2-hexenyl, β-methyl-4-(furo[3,2-c]pyridyl)-3 - butenyl, 5-(furo[3,2-c]pyridyl)-2,4-pentadienyl, 4-(furo[3,2-c]pyridyl)-1 ,3 - butadienyl, 6-(furo[3,2-c]pyridyl)-2,4-hexadienyl, 6-(furo[3,2-c]pyridyl)-3,5 - hexadienyl, 6-(furo[3,2-c]pyridyl)-1 ,3-hexadienyl, 5-(furo[3,2-c]pyridyl)-1 ,3 - pentadienyl, 2-quinolylvinyl, 3-(1 ,4-dihydroquinoly)l-2-propenyl, 4-benzo - thiazolyl-3-butenyl, 3-carbostyril-2-butenyl, 2-methyl-3-(3,4-dihydrocarbostyril) - 2-propenyl, 5-(1 ,2,3,4-tetraquinolyl)-4-petenyl, 5-indolyl-2-pentenyl, 6-indoiinyl ■ 5-hexenyl, 6-indolinyl-4-hexenyl, 6-benzoimidazolyl-3-hexenyl, 6-benzoxazolyl
2-hexenyl, β-methyl-4-isoquinolyl-3-butenyl, 5-quinazolidinyl-2,4-pentadienyl, 4-cinnolyl-1 ,3-butadienyl, 6-quinoxalinyl-2,4-hexadienyl, 6-phthalazinyl-3,5 - hexadienyl, 6-chromanyl-1 ,3-hexadienyl, 5-isoindolinyl-1 ,3-pentadienyl, 2-(4H - chromenyl)vinyl, 3-(2,3-dihydro-2-benzofuryl)-2-propenyl, 4-(2-perhydrobenzo - furyl)-3-butenyl, 3-(1 ,4-benzoxadinyl)-2-butenyl, 2-methyl-3-(3,4-dihydro-2H - 1 ,4-benzoxazinyl)-2-propenyl, 5-(1 ,4-benzothiazinyl)-4-pentenyl, 5-(1 ,2,3,4 - tetrahydroquinoxalinyl)-2-pentenyl, 6-(1 ,3-dithia-2,4-dihydronaphthalenyl)-5 - hexenyl, 6-(1 ,4-dithianaphthalenyl)-4-hexenyl, 6-(1 ,4-benzodioxanyl)-3 - hexenyl, 2-pyrrolidinylvinyl, 3-pyrrolidinyl-2-propenyl, 4-pyrrolidinyl-3-butenyl, 3-pyrrolidinyl-2-butenyl, 2-methyl-3-pyrrolidinyl-2-propenyl, 5-pyrrolidinyl-4 - pentenyl, 5-pyrrolidinyl-2-pentenyl, 6-pyrrolidinyl-5-hexenyl, 6-pyrrolidinyl-4 - hexenyl, 6-pyrrolidinyl-3-hexenyl, 6-pyrrolidinyl-2-hexenyl, β-methyl-4 - pyrrolidinyl-3-butenyl, 5-pyrrolidinyl-2,4-pentadienyl, 4-pyrrolidinyl-1 ,3 - butadienyl, 6-pyrrolidinyl-2,4-hexadienyl, 6-pyrrolidinyl-3,5-hexadienyl, 6 - pyrrolidinyl-1 ,3-hexadienyl, 5-pyrrolidinyl-1 ,3-pentadienyl, 2-piperidinylvinyl, 3 - piperidinyl-2-propenyl, 4-piperidinyl-3-butenyl, 3-piperidinyl-2-butenyl, 2 - methyl-3-piperidinyl-2-propenyl, 5-piperidinyl-4-pentenyl, 5-piperidinyl-2 - pentenyl, 6-piperidinyl-5-hexenyl, 5-piperidinyl-2-pentenyl, 6-piperidinyl-5 - hexenyl, 6-piperidinyl-4-hexenyl, 6-piperidinyl-3-hexenyl, 6-piperidinyl-2- hexenyl, β-methyl-4-piperidinyl-3-butenyl, 5-piperidinyl-2,4-pentadienyl, 4 - piperidinyl-1 ,3-butadienyl, 6-piperidinyl-2,4-hexadienyl, 6-piperidinyl-3,5 - hexadienyl, 6-piperidinyl-1 ,3-hexadienyl, 5-piperidinyl-1 ,3-pentadienyl, 2 - piperazinylvinyl, 3-piperazinyl-2-propenyl, 4-piperazinyl-3-butenyl, 3 - piperazinyl-2-butenyl, 2-methyl-3-piperazinyl-2-propenyl, 5-piperazinyl-4 - pentenyl, 5-piperazinyl-2-pentenyl, 6-piperazinyl-5-hexenyl, 6-piperazinyl-4 - hexenyl, 6-piperazinyl-3-hexenyl, 6-piperazinyl-2-hexenyl, β-methyl-4 - piperazinyl-3-butenyl, 5-piperazinyl-2,4-pentadienyl, 4-piperazinyl-1 ,3 - butadienyl, 6-piperazinyl-2,4-hexadienyl, 6-piperazinyl-3,5-hexadienyl, 6 - piperazinyl-1 ,3-hexadienyl, 5 piperazinyl-1 ,3-pentadienyl, 2-morpholinovinyl, 3 pyridyl-2-propenyl, 4-thienyl-3-butenyl, 3-pyradinyl-2-butenyl, 2-methyl-3 - pyrimidyl-2-propenyl, 2-pyridazinylvinyl, 3-pyrrolyl-2-propenyl, 4-imidazolyl-3 - butenyl, 3-imidazoly!-2-butenyl, 2-methyl-3-imidazolyl-2-propenyl, 5-imidazolyl ■ 4-pentenyl, 5-imidazolyl-2-pentenyl, 6-imidazolyl-5-hexenyl, 6-imidazolyl-4 - hexenyl, 6-imidazolyl-3-hexenyl, 6-imidazolyl-2-hexenyl, β-methyl-4-imidazolyl 3-butenyl, 5-imidazolyl-2,4-pentadienyl, 4-imidazolyl-1 ,3-butadienyl, 6 - imidazolyl-2,4-hexadienyl, 6-imidazolyl-3,5-hexadienyl, 6-imidazolyl-1 ,3 - hexadienyl, 5-imidazolyl-1 ,3-pentadienyl, 2-imidazolidinylvinyl, 3-pyrazolyl-1 ,3 • pentadienyl, 2-imidazolidinylvinyl, 3-pyrazolyl-2-propenyl, 4-pyrazolidinyl-3 - butenyl, 3-perhydrobenzofuryl-2-butenyl, 2-methyl-3-(1 ,3,4-oxadiazolyl)-2 - propenyl, 5-(1 ,2,4-triazolyl)-4-petenyl, 5-(1 ,2,3,4-tetrazolyl)-2-pentenyl, 6-(1 ,3,4 triazolyl)-5-hexenyl, 6-(1 ,2,4-oxadiazolyl)-4-hexenyl, 6-(2,3-dihydro-2 - benzofuryl)-3-hexenyl, 6-pyrrolinyl-2-hexenyl, β-methyl-5-nonyl-3-butenyl, 5 - isoxazolyl-2,4-pentadienyl, 4-thiazolyl-1 ,3-butadienyl, 6-thiazolidinyl-2,4 - hexadienyl, 6-(1 ,2,3,5-oxathiadiazolyl)-3,5-hexadienyl, 6-isothiazolyl-1 ,3 - hexadienyl, 5-pyranyl-1 ,3-pentadienyl, 2-oxazolylvinyl, 3-oxazolyl-2-propenyl, 4-oxazolyl-3-butenyl, 3-oxazolyl-2-butenyl, 2-methyl-3-oxazolyl-2-propenyl, 5 - oxazolyl-4-pentenyl, 5-oxazolyl-2-pentenyl, 4-oxazolyl-3-pentenyl, 6-oxazolyl-5 hexenyl, 6-oxazolyl-4-hexenyl, 6-oxazolyl-3-hexenyl, 6-oxazolyl-2-hexenyl, β - methyl-4-oxazolyl-3-butenyl, 5-oxazolyl-2,4-pentadienyl, 4-oxazolyl-1 ,3 - butadienyl, 6-oxazolyl-2,4-hexadienyl, 6-oxazolyl-3,5-hexadienyl, 6-oxazolyl- 1 ,3-hexadienyl, 5-oxazolyl-1 ,3-pentadienyl, 2-pyrazolylvinyl, 3-quinuclidinyl-2 - propenyl, 4-benzothiazolyl-3-butenyl, 3-carbostyril-2-butenyl, 2-methyl-3-(3,4 - dihydro[2,3-g]quinolyl)-2-propenyl, 5-(1 ,2,3,4-tetrahydrofuro[2,3-g]quinolyl)-4 - pentenyl, 2-(naphtho[2,1 -b]furyl)vinyl, 3-(naphtho[2,1 -b]furyl)-2-propenyl, 4 - (naphtho[2,1-b]furyl)-3-butenyl, 3-(naphtho[2,1-b]furyl)-2-butenyl, 2-methyl-3 -
(naphtho[2,1-b]furyl)-2-propenyl, 5-(naphtho[2,1 -b]furyl)-4-pentenyl, 5-(naphtho [2,1-b]furyl)-2-pentenyl, 4-(naphtho[2,1-b]furyl)-3-pentenyl, 6-(naphtho[2,1-b] - furyl)-5-hexenyl, 6-(naphtho[2,1 -b]furyl)-4-hexenyl, 6-(naphtho[2,1-b]furyl)-3 - hexenyl, 6-(naphtho[2,1-b]furyl)-2-hexenyl, β-methyl-4-(naphtho[2,1-b]furyl)-3 - butenyl, 5-(naphtho[2,1 -b]furyl)-2,4-pentadienyl, 4-(naphto[2,1 -b]furyl)-1 ,3 - butadienyl, 6-(naρhtho[2,1-b]furyl)-2,4-hexadienyl, 6-(naphtho[2,1 -b]furyl)-3,5 - hexadienyl, 6-(naphtho[2,1-b]furyl)-1 ,3-hexadienyl, 5-(naphtho[2,1 -b]furyl)-1 ,3 - pentadienyl, 2-(imidazo[1 ,2-a]pyridyl)vinyl, 3-(imidazo[1 ,2-a]pyridyl)-2 - propenyl, 4-(imidazo[1 ,2-a]pyridyl)-3-butenyl, and the like. The phenyl-lower alkoxycarbonyl group includes a phenylalkoxy - carbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1 -phenyl - ethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenyl - pentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1 ,1 -dimethyl-2-phenylethoxy - carbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.
The lower alkoxycarbonyloxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by alkoxycarbonyloxy group wherein the alkoxy moiety is a a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms , for example, methoxycarbonyloxymethyl, ethoxycarbonyloxy - methyl, 2-ethoxycarbonyloxyethyl, 1 -ethoxycarbonyloxyethyl, 3-methoxy - carbonyloxypropyl, 4-ethoxycarbonyloxybutyl, 6-propoxycarbonyloxyhexyl, 5 - isopropoxycarbonyloxypentyl, 1 ,1 -dimethyl-2-butoxycarbonyloxyethyl, 2-methyl • 3-tert-butoxycarbonyloxypropyl, 2-pentyloxycarbonyloxyethyl, hexyloxy - carbonyloxymethyl, and the like.
The benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring includes a straight chain or branched chain alkyl group having 1 to 6 carbon atom, which is substituted by a benzoyi group wherein the phenyl ring may optionally have 1 to 3 halogen substituents, for example, benzoylmethyl. 1-(2-chlorobenzoyl)ethyl, 2-(3-chlorobenzoyl) - ethyl, 3-(4-chlorobenzoyl)propoyl, 4-(2-fluorobenzoyl)butyl, 1 ,1-dimethyl-2-(3 - fluorobenzoyl)ethyl, 5-(4-fluorobenzoyl)pentyl, 6-(2-bromobenzoyl)hexyl, 2 - methyl-3-(3-bromobenzoyl)propyl, (4-bromobenzoyl)methyl, 2-(2-iodobenzoyl) - ethyl, 1-(4-iodobenzoyl)ethyl, (3,5-dichlorobenzoyl)methyl, 2-(2,6-dichloro - benzoyl)ethyl, 1-(3,4-dichlorobenzoyl)ethyl, 3-(3,4-difluorobenzoyl)propyl, (3,5 - dibromobenzoyl)methyl, (3,4,5-thchlorobenzoyl)methyl, and the like.
The amino group having optionally a lower alkanoyl substituent includes an amino group which may optionally have a substituent of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, t-butylcarbonylamino, hexanoylamino, and the like.
The present invention specifically includes the following compounds.
(1 ) A quinoxaline derivative of the formula (1 ) wherein R1 is hydrogen atom and R2, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(2) A quinoxaline derivative of the formula (1 ) wherein R1 is a halogen atom and R2, R3, R4, m, n and r are the same as defined above, or a salt thereof. (3) A quinoxaline derivative of the formula (1) wherein R1 is a lower alkyl group and R2, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(4) A quinoxaline derivative of the formula (1 ) wherein R2 is hydrogen atom and R1, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(5) A quinoxaline derivative of the formula (1 ) wherein R2 is a lower alkyl group having optionally a halogen substituent, and R1 , R3, R4, m, n and r are the same as defined above, or a salt thereof. (6) A quinoxaline derivative of the formula (1 ) wherein R2 is phenyl group and R1 , R3, R4, m, n and r are the same as defined above, or a salt thereof.
(7) A quinoxaline derivative of the formula (1 ) wherein R2 is a morpholino-substituted lower alkyl group and R1, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(8) A quinoxaline derivative of the formula (1 ) wherein R2 is an imidazolyl-substituted lower alkyl group and R1 , R3, R4, m, n and r are the same as defined above, or a salt thereof. (9) A quinoxaline derivative of the formula (1 ) wherein R3 is hydrogen atom, R4 is a group of the formula:
Figure imgf000045_0001
(wherein A, R5 and p are the same as defined above), and R1 , R2 and r are the same as defined above, or a salt thereof.
(10) A quinoxaline derivative of the formula (1 ) wherein R3 is a lower alkyl group, R4 is a group of the formula:
(R5)D
-* $
(wherein A, R5 and p are the same as defined above), and R1 , R2 and r are the same as defined above, or a salt thereof.
(1 1 ) A quinoxaline derivative of the formula (1 ) wherein R3 is hydrogen atom, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula:
-O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(12) A quinoxaline derivative of the formula (1 ) wherein R3 is a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(13) A quinoxaline derivative of the formula (1 ), wherein R3 is hydrogen atom, R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(14) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a lower alkenyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(15) A quinoxaline derivative of the formula (1), wherein R3 is hydrogen atom, R4 is a cycloalkyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(16) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (17) A quinoxaline derivative of the formula (1 ), wherein R3 is hydrogen atom, R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(18) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkyl group, R4 is a naphthyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(19) A quinoxaline derivative of the formula (1 ), wherein R3 is hydrogen atom, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(20) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(21 ) A quinoxaline derivative of the formula (1), wherein R3 is hydrogen atom, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (22) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(23) A quinoxaline derivative of the formula (1 ), wherein R3 is hydrogen atom, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(24) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(25) A quinoxaline derivative of the formula (1 ), wherein R3 is hydrogen atom, R4 is a phenoxy-substituted lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (26) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (27) A quinoxaline derivative of the formula (1), wherein R3 is hydrogen atom, R4 is a group of the formula:
Figure imgf000047_0001
(wherein the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(28) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a group of the formula:
Figure imgf000048_0001
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(29) A quinoxaline derivative of the formula (1), wherein R3 is hydrogen atom, R4 is a group of the formula: -As-CR^R^R4 (A5, R42, R43 and R44 are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(30) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a group of the formula: -A5-CR R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(31) A quinoxaline derivative of the formula (1), wherein R3 is hydrogen atom, R4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 - dihydro-1 H-indenyl ring, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(32) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro - 1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(33) A quinoxaline derivative of the formula (1), wherein R3 is hydrogen atom, R4 is a group of the
(R47)u formula:
Figure imgf000048_0002
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(34) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkyl group, R4 is a group of the formula:
Figure imgf000049_0001
(in which the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(35) A quinoxaline derivative of the formula (1), wherein R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (36) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogent atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000049_0002
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(37) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkenyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof.
(38) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
(39) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof. (40) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(41 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(42) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio-substitued lower alkyl group which may optinally have a lower alkoxy substituent on the phenyl moiety, and m, n, and r are the same as defined above, or a salt thereof.
(43) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(44) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(45) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof. (46) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000051_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(47) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R 3R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(48) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 - dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(49) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000051_0002
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(50) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is hydrogen atom, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(51 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
(R5)P
(in which A, R5 and p are t -he sa0me as defined above), and m, n and r are the same as defined above, or a salt thereof.
(52) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof. (53) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof. (54) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof. (55) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(56) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(57) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
(58) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(59) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(60) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000054_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(61 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(62) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3 - dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(63) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
, (R47)u
-®
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(64) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a lower alkyl group having optionally a halogen substituent, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group, and m, n and r are the same as defined above, or a salt thereof.
(65) A quinoxaline derivative of the formula (1), wherein R is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000055_0001
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(66) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R4° and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof. (67) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
(68) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(69) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(70) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(71 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
(72) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(73) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(74) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000056_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(75) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(76) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(77) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000057_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(78) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is phenyl group, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(79) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000057_0002
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(80) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof. (81 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
(82) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(83) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(84) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(85) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
(86) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(87) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(88) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000059_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof. (89) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof. (90) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro-1H - indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2, 3-dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(91 ) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000059_0002
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(92) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is a morpholino-substituted lower alkyl group, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4 - tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(93) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000060_0001
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof. (94) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR 0R41 (in which A4, R4° and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof.
(95) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
(96) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(97) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(98) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(99) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
(100) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(101 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(102) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000062_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(103) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -Aδ-CR^R^R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(104) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro-1 H - indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(105) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000062_0002
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(106) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group, R2 is an imidazolyl-substituted lower alkyl group, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4 - tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(107) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a group of the formula:
Figure imgf000063_0001
(wherein A, R5 and p are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof. (108) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alyl group, R4 is a group of the formula:
Figure imgf000063_0002
(wherein A, R5 and p are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof.
(109) A quinoxaline derivative of the formula (1 ), wherein R is hydrogen atom, R3 is hydrogen atom, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R2, m, n and r are the same as defined above, or a salt thereof.
(110) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -0-A4-CO-NR4OR41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R2, m, n and r are the same as defined above, or a salt thereof. (111 ) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a lower alkenyl group, and R2, m, n and r are the same as defined above, or a salt thereof. (1 2) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a lower alkenyl group, and R2, m, n and r are the same as defined above, or a salt thereof.
(113) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a cycloalkyl-lower alkyl group, and R2, m, n and r are the same as defined above, or a salt thereof.
(114) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and R2, m, n and r are the same as defined above, or a salt thereof.
(115) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a naphthyl-lower alkyl group, and
R2, m, n and r are the same as defined above, or a salt thereof.
(116) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a naphthyl-lower alkyl group, and R2, m, n and r are the same as defined above, or a salt thereof. (117) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R2, m, n and r are the same as defined above, or a salt thereof.
(118) A quinoxa ine derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R2, m, r and r are the same as defined above, or a salt thereof.
(119) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R is hydrogen atom, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R2, , n and r are the same as defined above, or a salt thereof.
(120) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen ator ■, R3 is a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R2, m, n and r are the same as defined above, or a salt thereof.
(121 ) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R2, m, n and r are the same as defined above, or a salt thereof.
(122) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R2, m, n and r are the same as defined above, or a salt thereof.
(123) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a phenoxy-substituted lower alkyl group, and R2, m, n and r are the same as defined above, or a salt thereof.
(124) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and R2, m, n and r are the same as defined above, or a salt thereof.
(125) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a group of the formula:
Figure imgf000065_0001
(wherein the symbols are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof.
(126) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a group of the formula:
Figure imgf000065_0002
(wherein the symbols are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof.
(127) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a group of the formula: -A5-CR 2R 3R44 (A5, R42, R43 and R44 are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof.
(128) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a group of the formula:
-A5-CR4 R 3R44 (A5, R42, R43 and R44 are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof.
(129) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a 2,3-dihydro-1 H-indenyl group - substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R2, m, n and r are the same as defined above, or a salt thereof.
(130) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a 2,3-dihydro-1 H-indenyl group substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R2, m, n and r are the same as defined above, or a salt thereof. (131 ) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom, R3 is hydrogen atom, R4 is a group of the formula:
Figure imgf000066_0001
(in which the symbols are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof.
(132) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 is a lower alkyl group, R4 is a group of the formula:
Figure imgf000066_0002
(in which the symbols are the same as defined above), and R2, m, n and r are the same as defined above, or a salt thereof. (133) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroquinolyl group which may optionally have a lower alkoxy group), and R2, m, n and r are the same as defined above, or a salt thereof. (134) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group and R2, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(135) A quinoxaline derivative of the formula (1),wherein R1 is an amino group having optionally a lower alkyl substituent and R2, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(136) A quinoxaline derivative of the formula (1), wherein R1 is an aminocarbonyl group having optionally a lower alkyl substituent and R2, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(137) A quinoxaline derivative of the formula (1), wherein R3 is a phenyl - lower alkoxycarbonyl group and R4 is a group of the formula:
Figure imgf000067_0001
(in which A, R5 and p are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(138) A quinoxaline derivative of the formula (1 ),wherein R3 is a lower alkanoyloxy-substituted lower alkyl group and R4 is a group of the formula:
Figure imgf000067_0002
(in which A, R5 and p are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(139) A quinoxaline derivative of the formula (1), wherein R3 is a phenyl - lower alkoxycarbonyl group and R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl ring selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R4 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(140) A quinoxaline derivative of the formula (1),wherein R3 is a lower alkanoyloxy-substituted lower alkyl group and R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl ring selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -0-A4-CO-NR4OR41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(141 ) A quinoxaline derivative of the formula (1 ),wherein R3 is a phenyl - lower alkoxycarbonyl group and R4 is a lower alkenyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (142) A quinoxaline derivative of the formula (1),wherein R3 is a lower alkanoyloxy-substituted lower alkyl group and R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(143) A quinoxaline derivative of the formula (1 ),wherein R3 is a phenyl - lower alkoxycarbonyl group and R4 is a cycloalkyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(144) A quinoxaline derivative of the formula (1 ),wherein R3 is a lower alkanoyloxy-substituted lower alkyl group and R4 is a cycloalkyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(145) A quinoxaline derivative of the formula (1 ),wherein R3 is a phenyl - lower alkoxycarbonyl group and R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(146) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group and R4 is a naphthyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(147) A quinoxaline derivative of the formula (1 ),wherein R3 is a phenyl lower alkoxycarbonyl group and R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(148) A quinoxaline derivative of the formula (1),wherein R3 is a lower alkanoyloxy-substituted lower alkyl group and R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl ring, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (149) A quinoxaline derivative of the formula (1 ),wherein R3 is a phenyl ■ lower alkoxycarbonyl group and R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(150) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(151 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a phenyl lower alkoxycarbonyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(152) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(153) A quinoxaline derivative of the formula (1 ), wherein R3 is a phenyl lower alkoxycarbonyl group, R4 is a phenoxy-substituted lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(154) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(155) A quinoxaline derivative of the formula (1 ), wherein R3 is a phenyl lower alkoxycarbonyl group, R4 is a group of the formula:
Figure imgf000070_0001
(wherein the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(156) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group, R4 is a group of the formula:
Figure imgf000070_0002
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(157) A quinoxaline derivative of the formula (1), wherein R3 is a phenyl - lower alkoxycarbonyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof. (158) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group, R4 is a group of the formula: -A5-CR4 R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof. (159) A quinoxaline derivative of the formula (1), wherein R3 is a phenyl - lower alkoxycarbonyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (160) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group, R4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(161 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a phenyl lower alkoxycarbonyl group, R4 is a group of the formula:
Figure imgf000071_0001
(in which the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (162) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyloxy-substituted lower alkyl group, R4 is a group of the formula:
Figure imgf000071_0002
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof. (163) A quinoxaline derivative of the formula (1) wherein R3 is a lower alkanoyl group, R4 is a group of the formula:
Figure imgf000071_0003
(wherein A, R5 and p are the same as defined above), and R1 , R2 and r are the same as defined above, or a salt thereof.
(164) A quinoxaline derivative of the formula (1) wherein R3 is a lower alkoxycarbonyl group, R4 is a group of the formula:
Figure imgf000071_0004
(wherein A, R5 and p are the same as defined above), and R1 , R2 and r are the same as defined above, or a salt thereof.
(165) A quinoxaline derivative of the formula (1) wherein R3 is a lower alkanoyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R4° and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(166) A quinoxaline derivative of the formula (1) wherein R3 is a lower alkoxycarbonyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula:
-O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(167) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl group, R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(168) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyl group, R4 is a lower alkenyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(169) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl group, R4 is a cycloalkyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (170) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyl group, R4 is a cycloalkyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(171 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl group, R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(172) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyl group, R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(173) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (174) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(175) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(176) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(177) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(178) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (179) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl group, R4 is a phenoxy-substituted lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (180) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyl group, R4 is a phenoxy-substituted lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (181 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl group, R4 is a group of the formula:
Figure imgf000074_0001
(wherein the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (182) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyl group, R4 is a group of the formula:
Figure imgf000074_0002
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(183) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(184) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (185) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl group, R4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 - dihydro-1 H-indenyl ring, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(186) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 - dihydro-1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(187) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl group, R4 is a group of the formula:
Figure imgf000075_0001
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(188) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyl group, R4 is a group of the formula:
Figure imgf000075_0002
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(189) A quinoxaline derivative of the formula (1 ) wherein R3 is a lower alkoxy-lower alkyl group, R4 is a group of the formula:
Figure imgf000075_0003
(wherein A, R5 and p are the same as defined above), and R1, R2 and r are the same as defined above, or a salt thereof. (190) A quinoxaline derivative of the formula (1 ) wherein R3 is phenoxycarbonyl group, R4 is a group of the formula:
Figure imgf000075_0004
(wherein A, R5 and p are the same as defined above), and R1 , R2 and r are the same as defined above, or a salt thereof.
(191 ) A quinoxaline derivative of the formula (1 ) wherein R3 is a lower alkoxy-lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula:
-O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(192) A quinoxaline derivative of the formula (1 ) wherein R3 is phenoxycarbonyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR 0R41 (in which A4, R40 and R4 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1 , R3, R4, m, n and r are the same as defined above, or a salt thereof.
(193) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(194) A quinoxaline derivative of the formula (1 ), wherein R3 is phenoxy - carbonyl group, R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(195) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above.
(196) A quinoxaline derivative of the formula (1 ), wherein R3 is phenoxycarbonyl group, R4 is a cycloalkyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (197) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (198) A quinoxaline derivative of the formula (1), wherein R3 is phenoxycarbonyl group, R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(199) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(200) A quinoxaline derivative of the formula (1), wherein R3 is phenoxycarbonyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(201 ) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy - lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (202) A quinoxaline derivative of the formula (1), wherein R3 is phenoxycarbonyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(203) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(204) A quinoxaline derivative of the formula (1 ), wherein R3 is phenoxycarbonyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(205) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(206) A quinoxaline derivative of the formula (1), wherein R3 is phenoxycarbonyl group, R4 is a phenoxy-substituted lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(207) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a group of the formula:
Figure imgf000078_0001
(wherein the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (208) A quinoxaline derivative of the formula (1 ), wherein R3 is phenoxycarbonyl group, R4 is a group of the formula:
Figure imgf000078_0002
(in which the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(209) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a group of the formula: -A5-CR42R 3R44 (A5,
R42, R43 and R44 are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(210) A quinoxaline derivative of the formula (1), wherein R3 is phenoxycarbonyl group, R4 is a group of the formula: -A5-CR4 R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(211 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(212) A quinoxaline derivative of the formula (1), wherein R3 is phenoxy- carbonyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 - dihydro-1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(213) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxy-lower alkyl group, R4 is a group of the formula:
Figure imgf000079_0001
(in which the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(214) A quinoxaline derivative of the formula (1 ), wherein R3 is phenoxy carbonyl group, R4 is a group of the formula:
Figure imgf000079_0002
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof. (215) A quinoxaline derivative of the formula (1 ) wherein R3 is a lower alkanoyl -substituted lower alkyl group, R4 is a group of the formula:
Figure imgf000079_0003
(wherein A, R5 and p are the same as defined above), and R1, R2 and r are the same as defined above, or a salt thereof.
(216) A quinoxaline derivative of the formula (1) wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a group of the formula:
,r- (R5)p →-0
(wherein A, R5 and p are the same as defined above), and R1 , R2 and r are the same as defined above, or a salt thereof. (217) A quinoxaline derivative of the formula (1) wherein R3 is lower alkanoyl-substituted lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1 , R3, R4, m, n and r are the same as defined above, or a salt thereof.
(218) A quinoxaline derivative of the formula (1) wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - calbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1 , R3, R4, m, n and r are the same as defined above, or a salt thereof.
(219) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(220) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a lower alkenyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(221 ) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and
R1, R2, m, n and r are the same as the same, or a salt thereof.
(222) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (223) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a naphthyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (224) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group group, R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(225) A quinoxaline derivative of the formula (1), wherein R3 is a lowe alkanoyl-substituted lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(226) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(227) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(228) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a phenylsulfinyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(229) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(230) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(231 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(232) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (233) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a group of the formula:
Figure imgf000082_0001
(wherein the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(234) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a group of the formula:
Figure imgf000082_0002
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(235) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a group of the formula:
-A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(236) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a group of the formula: -A5-CR42R 3R44 (A5, R42, R43 and R44 are the same as defined above), and
R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(237) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a 2, 3-dihydro-1 H-indenyl group- substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (238) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a 2,3-dihydro-1 H - indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2, 3-dihydro-1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(239) A quinoxaline derivative of the formula (1), wherein R3 is a lower alkanoyl-substituted lower alkyl group, R4 is a group of the formula:
Figure imgf000083_0001
(in which the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (240) A quinoxaline derivative of the formula (1 ), wherein R3 is a lower alkoxycarbonyloxy-substituted lower alkyl group, R4 is a group of the formula:
Figure imgf000083_0002
(in which the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (241 ) A quinoxaline derivative of the formula (1 ) wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a group of the formula:
Figure imgf000083_0003
(wherein A, R5 and p are the same as defined above), and R1 , R2 and r are the same as defined above, or a salt thereof.
(242) A quinoxaline derivative of the formula (1 ) wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a group of the formula:
Figure imgf000084_0001
(wherein A, R5 and p are the same as defined above), and R1, R2 and r are the same as defined above, or a salt thereof. (243) A quinoxaline derivative of the formula (1 ) wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -0-A4-CO-NR4°R i (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1, R3, R4, m, n and r are the same as defined above, or a salt thereof. (244) A quinoxaline derivative of the formula (1) wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1, R3, R4, m, n and r are the same as defined above, or a salt thereof.
(245) A quinoxaline derivative of the formula (1), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(246) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a lower alkenyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(247) A quinoxaline derivative of the formula (1 ), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a cycloalkyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(248) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a cycloalkyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (249) A quinoxaline derivative of the formula (1), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a naphthyl-lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(250) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a naphthyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(251 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(252) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(253) A quinoxaline derivative of the formula (1 ), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (254) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (255) A quinoxaline derivative of the formula (1 ), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof. (256) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (257) A quinoxaline derivative of the formula (1), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a phenoxy-substituted lower alkyl group, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(258) A quinoxaline derivative of the formula (1), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a phenoxy-substituted lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(259) A quinoxaline derivative of the formula (1), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring R4 is a group of the formula:
Figure imgf000087_0001
(wherein the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(260) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a group of the formula:
(R8)α
(in which the symbols are - th0e same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(261 ) A quinoxaline derivative of the formula (1), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(262) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR52R53 (in which E, R52 and R53 are the same as defined above), R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(263) A quinoxaline derivative of the formula (1 ), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(264) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula: -E-NR5 R53 (in which E, R52 and R53 are the same as defined above), R4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro -
1 H-indenyl ring, and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(265) A quinoxaline derivative of the formula (1), wherein R3 is a benzoyl-substituted lower alkyl group which may optionally have a halogen substituent on the phenyl ring, R4 is a group of the formula:
Figure imgf000088_0001
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof. (266) A quinoxaline derivative of the formula (1), wherein R3 is a group of the fomula: -E-NR52N53 (in which E, R52 and R53 are the same as defined above), R4 is a group of the formula:
Figure imgf000088_0002
(in which the symbols are the same as defined above), and R1 , R2, m, n and r are the same as defined above, or a salt thereof.
(267) A quinoxaline derivative of the formula (1 ) wherein R3 is a group of the formula:
—A R54
Figure imgf000088_0003
(in which A and R54 are the same as defined above), R4 is a group of the formula:
Figure imgf000088_0004
(in which A, R5 and p are the same as defined above), and R1, R2 and r are the same as defined above, or a salt thereof. (268) A quinoxaline derivative of the formula (1) wherein R3 is a group of the formula:
—A R54 =<
°Y o°
(in which A and R54 are the same as defined above), R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl - lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and R1, R3,
R4, m, n and r are the same as defined above, or a salt thereof.
(269) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
- -
Figure imgf000089_0001
(in which A and R54 are the same as defined above), R4 is a lower alkenyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (270) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
— 54
Figure imgf000089_0002
(in which A and R54 are the same as defined above), R4 is a cycloalkyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (271 ) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
Figure imgf000090_0001
(in which A and R54 are the same as defined above), R4 is a naphthyl-lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (272) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
— 54
Figure imgf000090_0002
(in which A and R54 are the same as defined above), R4 is a phenylthio - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a sa|t thereof. (273) A quinoxaline derivative of the formula (1), wherein R3 is a group of the formula:
— 54
Figure imgf000090_0003
(in which A and R54 are the same as defined above), R4 is a phenylsulfinyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof. (274) A quinoxaline derivative of the formula (1), wherein R3 is a group of the formula: — 54
Figure imgf000091_0001
(in which A and R54 are the same as defined above), R4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(275) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
Figure imgf000091_0002
(in which A and R54 are the same as defined above), R4 is a phenoxy - substituted lower alkyl group, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(276) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
Figure imgf000091_0003
(in which A and R54 are the same as defined above), R4 is a group of the formula:
Figure imgf000091_0004
(wherein the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(277) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
Figure imgf000092_0001
(in which A and R54 are the same as defined above), R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(278) A quinoxaline derivative of the formula (1 ), wherein R3 is a group of the formula:
Figure imgf000092_0002
(in which A and R54 are the same as defined above), R4 is a 2,3-dihydro-1 H - indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R1, R2, m, n and r are the same as defined above, or a salt thereof.
(279) A quinoxaline derivative of the formula (1), wherein R3 is a group of the formula:
—A R54
Figure imgf000092_0003
(in which A and R54 are the same as defined above), R4 is a group of the formula:
Figure imgf000092_0004
(in which the symbols are the same as defined above), and R1, R2, m, n and r are the same as defined above, or a salt thereof. (280) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
(in which A, R5 and p ar →e the- sa0me as defined above), and m, n and r are the same as defined above, or a salt thereof.
(281 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl - lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof.
(282) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
(283) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl - lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(284) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl - lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(285) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl - lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(286) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio - substitued lower alkyl group which may optinally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(287) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(288) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(289) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy - substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(290) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000095_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(291 ) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(292) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro -
1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof. (293) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000096_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(294) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is hydrogen atom, R3 and R4 combine together with the nitrogen atom to form
1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(295) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000096_0002
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(296) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR 0R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof.
(297) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof. (298) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(299) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(300) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(301 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof. (302) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof. (303) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(304) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000098_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(305) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(306) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 - dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(307) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
(R47)u
(in which the symbols a -re t0he same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(308) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a lower alkyl group having optionally a halogen substituent, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group, and m, n and r are the same as defined above, or a salt thereof.
(309) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000099_0001
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof. (310) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenyl - carbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof. (311 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof. (312) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof. (313) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof. (314) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio- substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(315) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
(316) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl - substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(317) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(318) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
~®
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(319) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(320) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro-1 H - indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(321 ) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
, (R47)u
-®
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(322) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is phenyl group, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4 - tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(323) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000103_0001
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(324) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula:
-0-A4-CO-NR4°R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof. (325) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
(326) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(327) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof. (328) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(329) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
(330) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(331 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(332) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000105_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(333) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(334) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a 2,3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro - 1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof. (335) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000105_0002
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(336) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is a morpholino-substituted lower alkyl group, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(337) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
(R5)P
-*-#
(in which A, R5 and p are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(338) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4> R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, and m, n and r are the same as defined above, or a salt thereof.
(339) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a lower alkenyl group, and m, n and r are the same as defined above, or a salt thereof.
(340) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a cycloalkyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(341 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a naphthyl-lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(342) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof. (343) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety and m, n and r are the same as defined above, or a salt thereof.
(344) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and m, n and r are the same as defined above, or a salt thereof.
(345) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a phenoxy-substituted lower alkyl group, and m, n and r are the same as defined above, or a salt thereof.
(346) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000108_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(347) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula: -As-CR^R^R 4 (A5, R42, R43 and R44 are the same as defined above), and m, n and r are the same as defined above, or a salt thereof.
(348) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a 2, 3-dihydro-1 H-indenyl group-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro ■ 1 H-indenyl ring, and m, n and r are the same as defined above, or a salt thereof.
(349) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 is hydrogen atom or a lower alkyl group, R4 is a group of the formula:
Figure imgf000109_0001
(in which the symbols are the same as defined above), and m, n and r are the same as defined above, or a salt thereof. (350) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent or an aminocarbonyl group having optionally a lower alkyl substituent, R2 is an imidazolyl-substituted lower alkyl group, R3 and R4 combine together with the nitrogen atom to form 1 ,2,3,4-tetrahydroisoquinolyl group which may optionally have a lower alkoxy group), and m, n and r are the same as defined above, or a salt thereof.
(351 ) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000110_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000110_0002
(in which the group _ . R47 and u are as defined above), and R2, m, n, and r are as defined above, or a salt thereof.
(352) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group. of the formula:
Figure imgf000111_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000111_0002
(in which A, R5 and p are as defined above), and R2, m, n, and r are as defined above, or a salt thereof.
(353) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000111_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A -CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and R2, m, n, and r are as defined above, or a salt thereof.
(354) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000112_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group; and R2, m, n, and r are as defined above, or a salt thereof.
(355) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000112_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group; and R2, m, n, and r are as defined above, or a salt thereof. (356) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000113_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group; and R2, m, n, and r are as defined above, or a salt thereof.
(357) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000113_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; and R2, m, n, and r are as defined above, or a salt thereof. (358) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000114_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; and R2, m, n, and r are as defined above, or a salt thereof.
(359) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000114_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; and R2, m, n, and r are as defined above, or a salt thereof.
(360) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000115_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group; and R2, m, n, and r are as defined above, or a salt thereof.
(361 ) A quinoxaline derivative of the formula (1 ), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000115_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000116_0001
(in which the group ( * > R8 ar,d q are as defined above); and R2, m, n,
and r are as defined above, or a salt thereof.
(362) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000116_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -As-CR^R^R44 (in which A5,
R42, R43 and R44 are as defined above); and R2, m, n, and r are as defined above, or a salt thereof.
(363) A quinoxaline derivative of the formula (1), wherein R1 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: — A R54
Figure imgf000117_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and R2, m, n, and r are as defined above, or a salt thereof. (364) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
- 54
Figure imgf000117_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000117_0003
(in which the group TV R47 ar|d u are as defined above), and m, n, and r
are as defined above, or a salt thereof. (365) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (jn which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000118_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000118_0002
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(366) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having otionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000118_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (367) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000119_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof. (368) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000120_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(369) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000120_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(370) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000121_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (371) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000121_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(372) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000122_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (373) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000122_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(374) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxy - carbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000123_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000123_0002
(in which the group __ . R8 and q are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(375) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxy - carbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000123_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof. (376) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxy carbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R$3 are as defined above), or a group of the formula:
—A R54
>=(
O O
Y o
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof. (377) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
>=<
O O
Y O
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000125_0001
(in which the group _ ) > R47 and u are as defined above), and m, n, and r are as defined above, or a salt thereof.
(378) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000125_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000125_0003
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(379) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000126_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (380) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E - N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
54
Figure imgf000126_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
(381) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000127_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(382) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000128_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(383) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
54
Figure imgf000128_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(384) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(385) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =
°Y o° (in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (381 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000130_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(387) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
X
°Y O°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000130_0002
(in which the group -Θ' R8 and q are as defined above), and m, n, and r are as defined above, or a salt thereof.
(388) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000131_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof. (389) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: — A R54
X
°Y O° (in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof. (390) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
- 54
Figure imgf000132_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000132_0002
(in which the group __ ~Λ , R47 and u are as defined above), and m, n, and
are as defined above, or a salt thereof. (391 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =<
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000133_0001
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(392) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 64
Figure imgf000133_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (393) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000134_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof. (394) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: — A R54
Figure imgf000135_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(395) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which
E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000135_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(396) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000136_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (397) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
O O
Y o
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(398) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000137_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (399) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000137_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(400) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000138_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000138_0002
(in which the group f~~ , R8 and q are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(401 ) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000138_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof. (402) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000139_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof. (403) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000139_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000140_0001
(in which the group _/~ , R47 and u are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(404) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000140_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000140_0003
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(405) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 ^X
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (406) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000141_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof. (407) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000142_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(408) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 64
Figure imgf000142_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(409) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 "X
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(410) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000143_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (411) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _ 54
Figure imgf000144_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(412) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000144_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof. (413) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: —A R54
Figure imgf000145_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000145_0002
(in which the group ^~ , R8 and q are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(414) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000146_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR4 R 3R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof. (415) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000146_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof. (416) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000147_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000147_0002
(in which the group _ 7 , R47 and u are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(417) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000147_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
_ t,-ζ (in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(418) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000148_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A -CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(419) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
°Y O°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof. (420) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000149_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof. (421 ) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000150_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(422) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53)
(in which E, R52 and R53 are as defined above), or a group of the formula:
— 4
Figure imgf000150_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (423) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: — 54
Figure imgf000151_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (424) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000151_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(425) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000152_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof. (426) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000152_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000152_0003
(in which the group R8 and q are as defined above), and m, n, and r
Figure imgf000152_0004
are as defined above, or a salt thereof.
(427) A quinoxaline derivative of the formula (1 ), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy- carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
>=
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof. (428) A quinoxaline derivative of the formula (1), wherein R1 is a halogen atom or a lower alkyl group; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
54
-A =<R
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof. (429) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E - N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
°Y o° (in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000154_0001
(in which the group T , R47 and u are as defined above), and m, n, and r are as defined above, or a salt thereof.
(430) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula:
-E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000155_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000155_0002
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(431 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000155_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (432) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000156_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
(433) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: — A R54
Figure imgf000157_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(434) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000157_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(435) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000158_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(436) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula:
-E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000158_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(437) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =(
°Y 0°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(438) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E - N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =<
°Y o° (in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(439) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000160_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000160_0002
(in which the group ~ , R8 and q are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(440) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000161_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof. (441) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is hydrogen atom; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl - substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _ 54
Figure imgf000161_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2, 3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof. (442) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000162_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000162_0002
(in which the group ^Tλ > R47 and u are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(443) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxy - carbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
-A R54
°γ o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000163_0001
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(444) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _ 54
Figure imgf000163_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(445) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000164_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
(446) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
X
°Y O°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(447) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000165_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(448) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy- carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: —A R54
Figure imgf000166_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(449) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =
°Y O°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(450) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
X
°Y O°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(451 ) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
54
—A R
Figure imgf000167_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(452) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: —A R54
Figure imgf000168_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000168_0002
(in which the group , R8 and q are as defined above), and m, n, and r
Figure imgf000168_0003
are as defined above, or a salt thereof.
(453) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R5 )(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000169_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof. (454) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a lower alkyl group having optionally a halogen substituent; R3 is a lower alkanoyloxy - substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy - carbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxy - carbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _ 54
Figure imgf000169_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof. (455) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000170_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000170_0002
(in which the group __ > R47 and u are as defined above), and m, n, and r are as defined above, or a salt thereof.
(456) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: °γ o° (in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000171_0001
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(457) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53)
(in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000171_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof. (458) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000172_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof. (459) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _ 54
Figure imgf000172_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(460) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000173_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(461 ) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000174_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(462) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(463) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000175_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(464) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53)
(in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000175_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(465) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 X
°Y O° (in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000176_0001
(in which the group , R8 and q are as defined above), and m, n, a d r
are as defined above -, o0 n
r a sa"lt thereof.
(466) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53)
(in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000176_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
(467) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is phenyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxy - carbonyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy - lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000177_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
(468) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000178_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000178_0002
(in which the group -© R47 and u are as defined above), and m, n, and r
are as defined above, or a sa•lt thereof.
(469) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000178_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000178_0004
(in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(470) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =(
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A -CO-NR40R41 (in which A4, R40 and R4 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(471 ) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000180_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
(472) A quinoxaline derivative of the formula (1), wherein R is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(473) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 "X
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(474) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000181_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(475) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000182_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(476) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: —A R54
Figure imgf000183_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(477) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _ 54
Figure imgf000183_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(478) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _ *
Figure imgf000184_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000184_0002
(in which the group ~ , R8 and q are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(479) A quinoxaline derivative of the formula (1), wherein R is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000184_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -As-CR^R^R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
(480) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is a morpholino-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: —A R54
Figure imgf000185_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
(481 ) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
°Y O°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000186_0001
(in which the group _ *\ , R47 and u are as defined above), and m, n, and r
are as defined above, or a salt thereof.
(482) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000186_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: /R5\ (in which A, R5 and p are as defined above), and m, n, and r are as defined above, or a salt thereof.
(483) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54 =(
°Y o°
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A -CO-NR40R41 (in which A4, R40 and R41 are as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(484) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000188_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a lower alkenyl group, and m, n, and r are as defined above, or a salt thereof.
(485) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000188_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a cycloalkyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(486) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000189_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same .as defined above); R4 is a naphthyl-lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(487) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in. which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000189_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(488) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
—A R54
Figure imgf000190_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(489) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: — 54
Figure imgf000191_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, and m, n, and r are as defined above, or a salt thereof.
(490) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: _A R54
Figure imgf000191_0002
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a phenoxy-substituted lower alkyl group, and m, n, and r are as defined above, or a salt thereof.
(491 ) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
Figure imgf000192_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula:
Figure imgf000192_0002
(in which the group 7^\ , R8 and q are as defined above), and m, n, and r
are as defined above -,® or a sa-lt thereof.
(492) A quinoxaline derivative of the formula (1), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula:
— 54
Figure imgf000192_0003
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a group of the formula: -A5-CR42R43R44 (in which A5, R42, R43 and R44 are as defined above), and m, n, and r are as defined above, or a salt thereof.
(493) A quinoxaline derivative of the formula (1 ), wherein R1 is a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent; R2 is an imidazolyl-substituted lower alkyl group; R3 is a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyloxy - substituted lower alkyl group, a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which E, R52 and R53 are as defined above), or a group of the formula: —A R54
Figure imgf000193_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); R4 is a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, and m, n, and r are as defined above, or a salt thereof.
The compound of the present invention also includes the compounds of the formula (1 ) wherein both m and n are simultaneously 1 , or m is 1 and n is 0, or m is 0 and n is 1 , or both m and n are simultaneously 0, but the more preferable compounds are compounds of the formula (1 ) wherein m is 1 and n is 0.
The heterocyclic group represented by the formula:
includes, for example, pyrid -yl,© thiazolyl, furyl, benzimidazolyl, benzothiazolyl, oxazolyl, quinolyl, indolyl, 1 ,4-benzodioxanyl, 3,4-dihydrofuro[2,3-g]quinolyl,
1 ,2,3,4-tetrahydrofuro[2,3-g]quinolyl, furo[3,2-c]pyridyl, furo[2.3-g]quinolyl, benzofuryl, benzothienyl, 2,3-dihydrobenzofuryl, perhydrobenzofuryl, imidazolyl, 1 ,2,3,4-tetrazolyl, imidazo[1 ,2-a]pyridyl, and the like. The heterocyclic group represented by the formula:
includes, for example, 1 ,2,3,4-t -etra©zolyl, thiazolyl, pyridyl, oxazolyl, 1 ,2,3,5 - oxathiadiazolyl, 1 ,3,4-triazolyl, 1 ,2,4-oxadiazolyl, 1 ,2,4-triazinyl, imidazolyl, 1 ,3,4-oxadiazolyl, pyrimidinyl, 1 ,2,3,4-tetrazolyl, 3,4-dihydrofuro[2,3-g]quinolyl, 1 ,2,3,4-tetrahydrofuro[2,3-g]quinolyl, naphtho[2,1-b]furyl, oxazolyl, furo[2,3 - g]quinolyl, and the like.
The heterocyclic group represented by the formula:
includes, for example, thiazolyl -, 1 ,©2,3,4-tetrazoiyl, thiazolidinyl, and the like.
The heterocyclic group represented by the formula:
-© includes, for example, benzofuryl, benzothiazolyl, carbostyril, 3,4 - dihydrocarbostyril, furo[3,2-c]pyridyl, benzothienyl, and the like.
The compounds of the present invention of the formula (1) may be prepared by various processes, but preferably prepared by the following processes. Reaction Scheme- 1
Figure imgf000195_0001
(2) (1)
[wherein R1, R2, R3, R4, r, m and n are the same as defined above]
The reaction of the compound (2) and the compound (3) is carried out by a conventional amido bond producing reaction. The amido bond producing reaction can be carried out under the same conditions as those of the conventional amino bond producing reaction, for example,
(a) a mixed acid anhydride process, i.e. a process of reacting the carboxylic acid compound (2) with an alkyl halocarbonate to form a mixed acid anhydride and reacting the resultant with the amine compound (3),
(b) an activated ester process, i.e. a process of converting the carboxylic acid compound (2) into an activated ester such as p-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester, etc., and reacting the resultant with the amine compound (3),
(c) a carbodiimide process, i.e. a process of condensing the carboxylic acid compound (2) and the amine compound (3) in the presence of an activating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole, etc.,
(d) other processes, i.e. a process of converting the carboxylic acid compound (2) into a carboxylic anhydride by treating it with a dehydrating agent such as acetic anhydride, and reacting the resultant with the amine compound (3); a process of reacting an ester of the carboxylic acid compound (2) with a lower alcohol and the amine compound (3); a process of reacting an acid halide compound of the carboxylic acid compound (2), i.e. a carboxylic acid halide, with the amine compound (3); a process of activating the carboxylic acid (2) with a phosphorus compound such as triphenylphosphine, diethyl chlorophosphate, etc., and reacting the resultant with the amine compound (3); a process of converting the carboxylic acid compound (2) into a N - carboxyamino anhydride with a phosgene or chloroformic acid trichloromethyl ester, and reacting the resultant with the amine compound (3); a process of activating the carboxylic acid compound (2) with an acetylene compound such as trimethylsilylethoxyacetylene, etc., and reacting the resultant with the amine compound (3), and the like. The mixed acid anhydride used in the above mixed acid anhydride process (a) is obtained by the known Schόtten-Baumann reaction, and the reaction product is used without isolating from the reaction mixture for the reaction with the amine compound (3) to give the desired compound (1) of the present invention. The Schόtten-Baumann reaction is usually carried out in the presence of a basic compound. The basic compound is any conventional compounds used for the Schόtten-Baumann reaction and includes, for example, organic basic compounds such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-methylmorpholine, 4-dimethylaminopyridine, 1 ,5 - diazabicyclo[4.3.0]nonene-5 (DBN), 1 ,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), etc., and inorganic basic compounds such as potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc. The reaction is usually carried out at a temperature from about -20°C to about 100°C, preferably at a temperature of 0°C to about 50°C, for about 5 minutes to about 10 hours, preferably for 5 minutes to about 2 hours.
The reaction between the mixed acid anhydride thus obtained and the amine compound (3) is usually carried out at a temperature of -20°C to about 150°C, preferably at a temperature of 10°C to about 50°C, for 5 minutes to about 10 hours, preferably for about 5 minutes to 5 hours. The mixed acid anhydride process is usually carried out in a solvent or without a solvent, and the solvent may be any conventional solvents which are usually used in the mixed acid anhydride process and includes, for example, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, dioxane, diisopropyl ether, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. 1 ,1 ,3,3-tetramethylurea, N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), or a mixture of these solvents. The alkyl halocarbonate used in the mixed acid anhydride process includes, for example, methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, isobutyl chloroformate, and the like. In said process, the carboxylic acid compound (2), the alkyl halocarbonate ester and the amine compound (3) are usually used in each equimolar amount, but preferably, the alkyl halocarbonate ester and the amine compound (3) are used each in an amount of about 1 to 1.5 mole to 1 mole of the carboxylic acid compound (2).
The activated ester process (b), for example, a process using N - hydroxysuccinic acid imide ester is carried out in a suitable solvent which does not affect the reaction, in the presence or absence of a basic compound.
Besides, the reaction may be carried out with addition of a condensing agent such as dicyclohexylcarbodiimide, carbonyldiimidazole, 1-ethyl-3-(3'-dimethyl - aminopropyl)carbodiimide, etc. The basic compound may be any basic compounds for the above mentioned Schόtten-Baumann reaction, and alkali metal carboxylates (e.g. sodium acetate, sodium benzoate, sodium formate, potassium acetate, lithium benzoate, cecium acetate, etc.), alkali metal halides (e.g. potassium fluoride, cecium fluoride, etc.), and the like. The solvent includes, for example, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethyl - phosphoric triamide, etc.), or a mixture of these solvents. The reaction is carried out at a temperature of 0 to 150°C, preferably at a temperature of 10 to 100°C for 5 to 30 hours. The amine compound (3) and N-hydroxysuccinic acid imide ester are used each at least in equimolar amount, preferably in an amount of 1 to 2 moles to 1 mole of the carboxylic acid compound (2).
Besides, the amido bond producing reaction in Reaction Scheme- 1 may also be carried out by reacting the carboxylic acid compound (2) and the amine compound (3) in the presence of a condensing agent such as phosphorus compounds (e.g. triphenylphosphine, triphenylphosphine-2,2' - dipyridyldisulfide, diethyl chlorophosphate, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl cyanophosphate, bis(2-oxo 3-oxazolidinyl)phosphinic chloride, etc.). The reaction is usually carried out in the presence of the solvent and the basic compound. The basic compound includes, for example, in addition to the basic compounds used for the above mentioned Schόtten-Baumann reaction, sodium hydroxide, potassium hydroxide, etc. The solvent includes, for example, in addition to the solvents used in the mixed acid anhydride process (a), pyridine, acetone, acetonitrile, or a mixture of two or more above solvents. The reaction is usually carried out at a temperature of -20°C to about 150°C, preferably at a temperature of 0°C to about 100°C, for about 5 minutes to about 30 hours. The condensing agent and the amine compound (3) are used at least in equimolar amount, preferably in an amount of about 1 to 2 moles, to 1 mole of the carboxylic acid compound
(2).
The amido bond producing reaction is also carried out by reacting the amine compound (3) and the carboxylic acid compound (2) in the presence of a condensing agent. The reaction is carried out in a suitable solvent in the presence or absence of a catalyst. The solvent includes, for example, halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), acetonitrile, dimethylformamide, etc. The catalyst includes, for example, organic bases such as dimethylaminopyridine, 4 - piperidinopyridine, etc., salts such as pyridinium tosylate, etc., camphorsulfonic acid, mercury oxide, and the like. The condensing agent includes, for example, acetylene compounds such as trimethylsilylethoxyacetylene, etc., and is used in an amount of 1 to 10 moles, preferably in an amount of 2 to 6 moles, to 1 mole of the amine compound (3). The carboxylic acid compound (2) is usually used at least in equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the amine compound (3). The reaction is usually carried out at a temperature of 0 to about 150°C, preferably at a temperature of room temperature to about 100°C, for about 1 to about 10 hours. Among the above other processes (d), in case of the process of reacting the carboxylic acid halide with the amine compound (3), the reaction is usually carried out in the presence of a de-hydrogen halogenating agent in an appropriate solvent. The de-hydrogen halogenating agent is any conventional basic compounds and includes, for example, in addition to the basic compounds used for the above mentioned Schόtten-Baumann reaction, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, and the like. The solvent includes, for example, in addition to the solvents used in the mixed acid anhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), pyridine, acetone, acetonitrile, or a mixture of two or more these solvents, and the like. The amount of the amine compound (3) and the carboxylic acid halide is not critical, but the amine compound (3) is usually used at least in equimolar amount, preferably about 1 to 5 moles, to 1 mole of the carboxylic acid halide. The reaction is usually carried out at a temperature of about
-20°C to about 180°C, preferably at a temperature of about 0°C to about 150°C, for about 5 minutes to about 30 hours.
The carboxylic acid halide used in the above reaction may be prepared, for example, by reacting the carboxylic acid compound (2) with a halogenating agent in a solvent or without a solvent. The solvent may be any one which does not affect the reaction, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. chloroform, methylene chloride, carbon tetrachloride, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, etc.), dimethylformamide, dimethylsulfoxide, and the like. The halogenating agent may be any conventional one which convert the hydroxy group in carboxyl group into a halogen, for example, thionyl chloride, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, phosphorus pentabromide, etc. The amount of the carboxylic acid compound (2) and the halogenating agent is not critical, but the halogenating agent is usually used in an excess amount to the carboxylic acid compound (2) when the reaction is carried out without a solvent, and when the reaction is carried out in a solvent, the hydrogenating agent is usually used at least in equimolar amount, preferably in an amount of 2 to 4 moles, to 1 mole of the carboxylic acid compound (2). The reaction temperature and the reaction period are not necessarily specified, but the reaction is usually carried out at a temperature of room temperature to about 100°C, preferably at a temperature of 50 to 80°C, for 30 minutes for about 6 hours. In the process of reacting the amine compound (3) with an ester of the carboxylic acid compound (2) and a lower alcohol, the reaction is carried out in a suitable solvent or without a solvent. The solvent may be any ones which are used in the above mentioned reaction of the carboxylic acid halide and the amine compound (3). The amine compound (3) is usually used at least in equimolar amount, preferably in an amount of 1 to 15 moles, to 1 mole of the ester of the carboxylic acid compound (2) and a lower alcohol. The reaction is usually carried out at a temperature of room temperature to 150°C, preferably at a temperature of room temperature to about 120°C, for one to about 20 hours. Reaction Scheme-2
Figure imgf000200_0001
(1a) (1 b)
[wherein R1, R2, r, m and n are the same as defined above, X is a halogen atom, R3a is hydrogen atom, a lower alkyl group, a phenyl-lower alkoxy - carbonyl group, a lower alkanoyloxy-substituted lower alkyl group, e) a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxy-lower alkyl group, a phenoxycarbonyl group, a lower alkanoyl-substituted lower alkyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a benzoyi - substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-NR52R53 (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula:
-CO-A- (in which A is a lower alkylene group)), a group of the formula:
Figure imgf000201_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above), a group of the formula:
Figure imgf000201_0002
(in which A, R5 and p are the same as defined above), a phenyl-lower alkenyl group which may optionally have a substituent on the phenyl moiety selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent, an alkenyl group, a cycloalkyl-lower alkyl group, a naphthyl-lower alkyl group, a phenylthio-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, a phenoxy-substituted lower alkyl group, a group of the formula:
Figure imgf000202_0001
(in which a group of the formula: R8 and p are the same as defined
Figure imgf000202_0002
above), a group of the formula: -A5-CR4 R43R44 (in which A5, R42, R43 and R44 are the same as defined above), a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent on the 2,3-dihydro-1 H-indenyl ring selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent, or a group of the formula:
Figure imgf000202_0003
(in which a group of the formula: __f . R47 and u are the same as defined
above, R3b is the same groups for the above mentioned R3a except hydrogen atom, and R3c and R3d are each hydrogen atom or a lower alkyl group]
The reaction of the compound (1a) and the compound (4a) is usually carried out in the presence or absence of a basic compound in a suitable inert solvent. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether, etc.), alcohols (e.g. methanol, ethanol, isopropanol, butanol, etc.), ethyl acetate, acetone, acetonitrile, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, or a mixture of these solvents. The basic compound includes, for example, an alkali metal carbonate (e.g. sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.), an alkali metal hydroxide (e.g. sodium hydroxide, potassium hydroxide, etc.), sodium hydride, potassium, sodium, sodium amide, an alkali metal alcoholate (e.g. sodium methylate, sodium ethylate, etc.), organic basic compounds (e.g. pyridine, N - ethyldiisopropylamine, dimethylaminopyridine, triethylamine, DBN, DBU, DABCO, etc.), and the like. The amount of the compound (1a) and the compound (4a) is not critical, but the compound (4a) is used at least in equimolar amount, preferably in an amount of 1 to 10 moles, to 1 mole of the compound (1a). The reaction is usually carried out at a temperature of 0 to about 200°C, preferably at a temperature of 0 to about 170°C, for 30 minutes to
30 hours. The reaction may be carried out by adding an alkali metal halide compound such as sodium iodide, potassium iodide, etc., into the reaction system. Further, the reaction may be carried out by adding a halogenated ammonium such as tetra-n-butylammonium iodide, tetra-n-butylammonium bromide, n-butyl triethyl ammonium iodide, tetraethylammonium iodide, tri-n - butyl methyl ammonium iodide, etc., into the reaction system.
The reaction of the compound (1a) and the compound (4b) is usually carried out in the presence of a reducing agent in a suitable solvent or without a solvent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, butanol, etc.), acetonitrile, formic acid, acetic acid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture of these solvents. The reducing agent includes, for example, formic acid, alkali metal salts of fatty acid (e.g. sodium formate, etc.), hydrogenating-reducing agents (e.g. sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, etc.), catalytic reducing agents (e.g. palladium-black, palladium - carbon, platinum oxide, platinum black, Raney-nickel, etc.), and the like.
When formic acid is used as a reducing agent, the reaction is usually carried out at a temperature of room temperature to about 200°C, preferably at a temperature of 50 to about 150°C, for 1 to about 10 hours. The formic acid is used in an excess amount to the compound (1a).
When a hydrogenating agent is used, the reaction is usually carried out at a temperature of -30 to about 100°C, preferably at a temperature of 0 to about 70°C, for 30 minutes to about 15 hours. The reducing agent is used in an amount of 1 to 20 moles, preferably in an amount of 1 to 6 moles, to 1 mole of the compound (1a). When lithium aluminum hydride is used as an reducing agent, the solvent may preferably ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, diglyme, etc.) and aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.).
When a catalytic reducing agent is used, the reaction is usually carried out under atmospheric pressure or 20 atms. of hydrogen gas, preferably under atmospheric pressure or about 10 atms. of hydrogen gas, or in the presence of a hydrogen-donor such as formic acid, ammonium formate, cyclohexene, hydrazine hydrate, etc., at a temperature of -30 to about 100°C, preferably at a temperature of 0 to about 60°C, for 1 to 12 hours. The catalytic reducing agent is usually used in an amount of 0.1 to 40 % by weight, preferably 1 to 20 % by weight, to the compound (1a). The compound (4b) is usually used at least in equimolar amount, preferably in an amount of 1 to excess amount, to 1 mole of the compound (1a). Reaction Scheme-3
Figure imgf000204_0001
(1c) (1d)
Figure imgf000204_0002
(1e) (1f)
[in which R1 , R2, R3, R4, r, m and n are the same as defined above] The reaction of converting the compound (1c) into the compound
(1d), and the reaction of converting the compound (1 e) into the compound (1f) are carried out in the presence of an oxidizing agent in a suitable solvent. The solvent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenated hydrocarbons (e.g. chloroform, dichloromethane, etc.), or a mixture of these solvents. The oxidizing agent includes, for example, peracids (e.g. performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloro - perbenzoic acid, p-carboxyperbenzoic acid, etc.), hydrogen peroxide, sodium metaperiodate, dichromic acid, dichromates (e.g. sodium dichromate, potassium dichromate, etc.), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate, etc.), lead salts (e.g. lead tetraacetate, etc.), and the like. The oxidizing agent is usually used at least in equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the starting compound. The above reaction is usually carried out at a temperature of -10 to 40°C, preferably at a temperature of -10°C to room temperature, for about 1 to 100 hours.
Reaction Scheme-4
Figure imgf000206_0001
[wherein R1 , R2, R3a, R8, a group of the formula: _/~~ , r, m, n, X and I are
the same as defined above, R9a is hydrogen atom, a lower alkanoyl group, a lower alkyl group, a morpholinocarbonyl-lower alkyl group, a cycloalkyl - carbonyl group, a phenyl-lower alkenylcarbonyl group, a lower alkylsulfonyl group, an aminocarbonyl group which may optionally have a lower alkyl substituent, a phenylsulfonyl group which may optionally have a lower alkyl substituent on the phenyl moiety, a phenyl-lower alkenyl group, a benzoyi • group which may optionally have 1 to 3 substituents on the phenyl moiety selected from a halogen atom, a lower alkoxy group, an amino group having optionally a lower alkanoyl substituent and hydroxy group, an amino- substituted lower alkanoyl group which may optionally have a lower alkanoyl substituent, an amino-substituted sulfonyl group which may optionally have a lower alkyl substituent, a phenyl-lower alkyl group, phenyl group and an amino group which may optionally have a lower alkanoyl substituent, R10a is a lower alkanoyl group, a cycloalkylcarbonyl group, a phenyl-lower alkenylcarbonyl group, a benzoyi group which may optionally have 1 to 3 substituents on the phenyl moiety selected from a halogen atom, a lower alkoxy group, an amino group having optionally a lower alkanoyl substituent and hydroxy group, and an amino-substituted lower alkanoyl group which may optionally have a lower alkanoyl substituent, R10 is a lower alkyl group, a morpholinocarbonyl-lower alkyl group, a lower alkenylsulfonyl group, an aminocarbonyl group which may optionally have a lower alkyl substituent, a phenylsulfonyl group which may optionally have a lower alkyl substituent, a phenyl-lower alkenyl group, an amino-substituted sulfonyl group which may optionally have a lower alkyl substituent, or a phenyl-lower alkyl group, q' is 1 or 2, R10c and R10d are each hydrogen atom or a lower alkyl group]
The reaction of the compound (1g) and the compound (5) is carried out under the same conditions as those of the reaction of the compound (2) and the compound (3) in the above mentioned Reaction Scheme-1. The compound (1h) wherein R10a is a lower alkanoyl group may be derived from the compound (1g) by subjecting the compound (1g) to lower alkanoylization with using a compound of the formula: (R11)20 (7) or R11X (8)
(in which R11 is a lower alkanoyl group, and X is the same as defined above). The lower alkanoylization reaction is carried out in the presence or absence of a basic compound. The basic compound includes, for example, an alkali metal (e.g. sodium, potassium, etc.), hydroxides, carbonates and hydrogen carbonates of these alkali metals, or organic basic compounds (e.g. N,N - dimethylaminopyridine, pyridine, piperidine, etc.), and the like. The reaction is carried out in a solvent or without a solvent. The solvent includes, for example, ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. diethyl ether, dioxane, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), water, pyridine, and the like. The compound (7) or the compound (8) is used at least in equimolar amount, preferably in an amount of 1 to excess amount, to 1 mole of the starting compound (1g). The reaction is carried out at a temperature of 0 to 200°C, preferably at a temperature of 0 to 150°C, for about 5 minutes to about 5 days.
The reaction of the compound (1g) and the compound (6a) or the compound (6b) is carried out under the same conditions as those of the reaction of the compound (1a) and the compound (4a) or the compound (4b) in the above mentioned Reaction Scheme-2. Reaction Scheme-5
Figure imgf000208_0001
[wherein R1, R2, R8, R3a, m, n, q', R9, R10, r and the group of the formula: __ "~*\ are the same as defined above, and R12 is a lower alkyl group]
The hydrolysis of the compound (1j) is carried out in the presence of an acid or a basic compound in a suitable solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), dimethylformamide, or a mixture of these solvents. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), and organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.). The basic compound includes, for example, alkali metal salts (e.g. sodium carbonate, potassium carbonate, etc.), alkali metal or alkaline earth metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature of room temperature to about 200°C, preferably at a temperature of room temperature to about 150°C, for 10 minutes to about 25 hours.
The reaction of the compound (1k) and the compound (9) is carried out under the same conditions as for the reaction of the compound (2) and the compound (3) in the above mentioned Reaction Scheme-1.
Reaction Scheme-6
Figure imgf000210_0001
(1n)
[wherein R1, R2, R3a, R8, m, n, q', X and the group of the formula: /""""N are
the same as defined above, R13 is a lower alkyl group, a phenyl-lower alkyl group which may optionally have an amino substituent having optionally a lower alkanoyl substituent on the phenyl moiety, a carboxy-substituted lower alkyl group, a lower alkoxycarbonyl-substituted lower alkyl group, a lower alkoxy-substituted lower alkyl group, a lower alkenyl group, a lower alkanoyl group, or a morpholinocarbonyl-lower alkyl group, and R14 is a lower alkoxy group, a phenyl-lower alkoxyl group which may optionally have an amino substituent having optionally a lower alkanoyl substituent on the phenyl moiety, a lower alkanoyloxy group or a lower alkoxy-substituted lower alkoxy group]
The reaction of converting the compound (1o) into the compound (1 m) is carried out by reducing the compound (1o) when R14 is a phenyl-lower alkoxy group. The reduction reaction is carried out by subjecting the compound (1 m) to catalytic hydrogenation in the presence of a catalyst in a suitable solvent . The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture of these solvents. The catalyst is, for example, palladium, palladium-black, palladium - carbon, platinum, platinum oxide, copper chromite, Raney-nickel, etc. and used in an amount of 0.02 to 1 part by weight to 1 part by weight of the compound (7). The reaction is usually carried out at a temperature of -20 to 100°C, preferably at a temperature of 0 to about 80°C, under 1 to 10 atms of hydrogen gas, for 0.5 to 20 hours.
The reaction of converting the compound (1 o) into the compound (1 m) is carried out by subjecting the compound (1o) to hydrolysis when R14 is a lower alkoxy group or a lower alkoxy-substituted lowre alkoxy group. The hydrolysis is carried out in the presence of an acid in a suitable solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polar solvents (e.g. acetonitrile, etc.), or a mixture of these solvents. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), fatty acids (e.g. formic acid, acetic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, potassium iodide, etc.), a mixture of the above Lewis acid and a iodide, and the like. The reaction is usually carried out at a temperature of 0 to 150°C, preferably at a temperature of room temperature to 100°C, for 0.5 to about 50 hours.
The reaction of converting the compound (1o) into the compound (1 m) is carried out in the same manner as in the hydrolysis of the compound (1j) in the above mentioned Reaction Scheme-5, when R14 is a lower alkanoyloxy group.
The reaction of the compound (1m) into the compound (10) is carried out under the same conditions as those of the reaction of the compound (1g) and the compound (6) in the above mentioned Reaction Scheme-4. The compound (1 n) wherein R13 is a lower alkanoyl group is also prepared by reacting the compound (1m) and the compound (7) under the same conditions as those of the reaction of the compound (1g) and the compound (7) in the above mentioned Reaction Scheme-4. Reaction Scheme-7
Figure imgf000212_0001
dP) (1q)
Figure imgf000212_0002
(1 E) (1F)
[wherein R1 , R2, R3a, R5, R8, m, n, q', A, X, r and the group of the formula:
"""N are the same as defined above, and p' is 1 or 2]
The halogenation reaction of the compound (1p) or the compound (1 E) is carried out in the presence of a conventional halogenating agent. The halogenating agent may be any conventional ones, for example, a halogen atom (e.g. bromine, chlorine, etc.), or halogenating agents such as iodine monochloride, sulfuryl chloride, N-halogenosuccinimides (e.g. N-bromo - succinimide, N-chlorosuccinimide, etc.). The halogenating agent is used at least in equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole o the compound (1 p) or the compound (1 E). The solvent includes, for example, halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), acetic acid, propionic acid, water, or a mixture of these solvents. The reaction is carried out at a temperature of 0°C to a boiling point of the solvent to be used, preferably at a temperature of 0 to 100°C, for 1 to about 10 hours.
Reaction Scheme-8
Figure imgf000214_0001
(1u) (1r) tl
Figure imgf000214_0002
[wherein R1, R2, R3a, R8, m, n, q', X, r, and the compound of the formula:
are the same as defined above, R15 is a lower alkyl group having a
Figure imgf000214_0003
hydroxy substituent, R16 is a lower alkanoyl group, R17 and R18 are each a lower alkyl group, R19 is a lower alkanoyloxy-substituted lower alkyl group,
Riβa is a hydrogen atom or a lower alkyl group, R18c is phenyl group, and R18b is a lower alkyl group] The reaction of converting the compound (1r) into the compound
(1s) is carried out in the presence of an oxidizing agent in a suitable solvent. The oxidizing agent includes, pyridinium chromates (e.g. pyridinium chloro - chromate, pyridinium dichlorochromate, etc.), dimethylsulfoxide-oxazolyl - chloride, manganese dioxide, DDQ, chromic acid, chromites (e.g. sodium chromite, potassium chromite, etc.), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate, etc.), and the like. The solvent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenated hydrocarbons (e.g. chloroform, dichloromethane, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, dioxane, etc.), dimethylosulfoxide, dimethyl - formamide, or a mixture of these solvents. The oxidizing agent is usually used at least in equimolar amount, preferably in an amount of 1 to 30 moles, to 1 mole of the starting compound. The reaction is carried out at a temperature of 0 to 150°C, preferably at a temperature of 0 to 100°C, for 1 to about 10 hours.
The reaction of converting the compound (1 r) into the compound (1s) is carried out by reacting the compound (1r) with an oxidizing agent in the presence of a co-oxidizing agent in a suitable solvent. The solvent includes, pyridine, ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), esters (e.g. ethyl acetate, etc.), water, alcohols (e.g. methanol, ethanol, isopropanol, t-butanol, etc.), or a mixture of these solvents. The co-oxidizing agent used therein includes, for example, N-oxides of organic amine such as pyridine N-oxide, N-ethyldiisopropylamine N-oxide, N-methylmorpholine N - oxide, trimethylamine N-oxide, triethylamine N-oxide, etc. The oxidizing agent includes, for example, tetra(n-propyl)ammonium perruthenate, and the like.
The co-oxidizing agent is used at least in equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the starting compound. The oxidizing agent is used in a catalytic amount. The reaction is carried out at a temperature of -20 to 150°C, preferably at a temperature of 0 to 100°C, for 1 to about 20 hours. The reaction may proceed more advantageously by adding Molecular Shieves into the reaction system.
The reaction of converting the compound (1s) into the compound (1 r) is carried out by a reduction reaction using a hydrogenating agent. The hydrogenating agent includes, for example, lithium aluminum hydride, diboran, aluminum diisobutyl hydride, sodium borohydride, lithium borohydride, tetrabutylammonium borohydride, calcium borohydride, aluminum hydride, and the like, and is used at least in 0.1 mole amount, preferably in an amount of 0.1 to 15 moles, to 1 mole of the starting compound. The reduction reaction is usually carried out in a suitable solvent, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture of these solvents, at a temperature of -60 to 150°C, preferably at a temperature of -30 to 100°C, for about 10 minutes to about 20 hours.
The reaction of the compound (1s) and the compound (11) is carried out in a suitable solvent. The solvent includes any solvents used for the Grignard reaction, and preferable ones are, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), saturated hydrocarbons (e.g. pentane, hexane, heptane, cyclohexane, etc.), and the like. The compound (11) is usually used at least in equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound (1s). The reaction is carried out at a temperature of -70 to 100°C, preferably at -30 to about 70°C, for 1 to about 50 hours.
The reaction of converting the compound (1 r) into the compound (1u) is carried out by reacting the compound (1r) with the compound (7) or the compound (8) under the same conditions as those of the reaction of the compound (1h) and the compound (7) or the compound (8) in the above mentioned Reaction Scheme-4.
The reaction of converting the compound (1u) into the compound (1 r) is carried out under the same conditions as those of the hydrolysis of the compound (1j) in the above mentioned Reaction Scheme-5.
The reaction of the compound (1s) and the compound (11a) is carried out in the presence of a basic compound in a suitable solvent. The basic compound includes, for example, inorganic bases such as metal sodium, metal potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, and organic bases such as alkali metal alcoholates (e.g. sodium methylate, sodium ethylate, potassium t-butoxide, etc.), an alkyl lithium, aryl lithium or lithium amide (e.g. methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropylamide, etc.), pyridine, piperidine, quinoline, triethylamine, N,N-dimethylaniline, and the like. The solvent may be any one which does not affect the reaction, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), or a mixture of these solvents. The reaction is usually carried out at a temperature of -80 to 150°C, preferably at a temperature of -80 to about 120°C, for 0.5 to about 15 hours. The compound (11a) is used at least in equimolar amount, preferably in an amount of 1 to 10 moles, to 1 mole of the compound (1s). Reaction Scheme-9
Figure imgf000217_0001
(1w) [wherein R1, R2, R3a, R5, m, n, p', A, r and X are the same as defined above,
R20 is a lower alkyl group, a lower alkoxy-substituted lower alkyl group, a lower alkenyl group, a lower alkoxycarbonyl-substituted lower alkyl group, a hydroxy - substituted lower alkyl group, a carboxy-substituted lower alkyl group, a phenyl ■ lower alkyl group which may optionally have a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety, a morpholino substituted lower alkyl group, or a group of the formula: -A-(-CO-NR6R7 (in which A*] , R6 and R7 are the same as defined above), and R21 is a lower alkoxy group, a lower alkoxy group-substituted lower alkoxy group, or a phenyl-lower alkoxy group which may optionally have a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety]
The reaction of converting the compound (1x) into the compound (1x') is carried out under the same conditions as those of the reaction of converting the compound (1 o) into the compound (1 m) in the above mentioned Reaction Scheme-6.
The reaction of the compound (1x') and the compound (12) is carried out under the same conditions as those of the reaction of the compound (1 m) and the compound (10) in the above mentioned Reaction Scheme-6.
Reaction Scheme-10a
Figure imgf000219_0001
(1A)
Reaction Scheme-10b
Figure imgf000219_0002
(1D)
[wherein R1 , R3a, R8, m, n, q', R5, p', r and the group of the formula: -© are the same as defined above, R22 is a lower alkoxycarbonyl-substituted lower alkoxy group, R23 is a carboxy-substituted lower alkoxy group, R24 is a morpholinocarbonyl-lower alkoxy group, R25 is a group of the formula:
-0-ArCO-NR6R7 (in which A f R6 and R7 are the same as defined above)] The reaction of converting the compound (1y) into the compound
(1z) and the reaction of converting the compound (1 B) into the compound (1C) are carried out under the same conditions as those of the hydrolysis of the compound (1j) in the above mentioned Reaction Scheme-5.
The reaction of the compound (1z) and the compound (13) and the reaction of the compound (1C) and the compound (14) are carried out under the same conditions as those of the reaction of the compound (2) and the compound (3) in the above mentioned Reaction Scheme- 1. Reaction Scheme- 11
Figure imgf000220_0001
0J) (1G)
Figure imgf000220_0002
(1H) OI)
[wherein R1 , R2, R8, R3a, m, n, q', R 2, R5, p', A, r and the group of the formula: •"" are the same as defined above] —( A3 )
The reaction of converting the compound (1j) into the compound (1G) and the compound of converting the compound (1 H) into the compound (11) are carried out under the same conditions as those of the reaction of converting the compound (1s) into the compound (1 r) in the above mentioned Reaction Scheme-8. Reaction Scheme-12
Figure imgf000221_0001
(1M)
(1L)
[wherein R1 , R2, R3a, R5, A, m, n, p', R12, r and X are the same as defined above and B is a lower alkylene group]
The reaction of converting the compound (1J) into the compound (1 K) is carried out under the same conditions as those of the reaction of converting the compound (1s) into the compound (1 r) in the above mentioned
Reaction Scheme-8.
The reaction of converting the compound (1 K) into the compound
(1 L) is carried out by reacting the compound (1 K) with a halogenating agent in a suitable solvent or without a solvent. The halogenating agent includes, for example, inorganic acids (e.g. hydrochloric acid, hydrobromic acid, etc.), N,N - diethyl-1 ,2,2-trichlorovinylamide, phosphorus pentachloride, phosphorus pentabromide, phosphorus oxychloride, thionyl chloride, mesyl chloride, tosyl chloride, etc., and a basic compound, carbon tetrachloride or carbon tetrabromide and triphenylphosphine. The basic compound may be the same as the above mentioned basic compounds for the reaction of the carboxylic halide and the amine compound in Reaction Scheme-1. The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. chloroform, methylene chloride, carbon tetrachloride, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), and the like. When a phenyl-lower alkyl halide (e.g. tosyl chloride, etc.) and a basic compound are used as a halogenating agent, the halogenating agent is used at least in equimolar amount, preferably in 1 to 2 moles, to 1 mole of the compound (1 K). When other halogenating agents are used, the halogenating agent is used at least in equimolar amount, preferably in an excess amount, to 1 mole of the compound (1 K). The reaction is usually carried out at a temperature of room temperature to 150°C, preferably at a temperature of room temperature to 80°C, for 1 to about 80 hours.
The reaction of the compound (1L) and the compound (13) is carried out under the same conditions as those of the reaction of the compound (1a) and the compound (4a) in the above mentioned Reaction Scheme-2.
Reaction Scheme- 13
Figure imgf000223_0001
(1P)
[wherein R1, R2, R3a, r, m and n are the same as defined above, R26 is a phenylthio-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, R27 is a phenylsulfinyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, and R28 is a phenylsulfonyl-substituted lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety]
The reaction of converting the compound (1 N) into the compound (10) and the reaction of converting the compound (10) into the compound (1 P) are carried out under the same conditions as those of the reaction of converting the compound (1c) into the compound (1d) in the above mentioned Reaction Scheme-3.
The reaction of converting the compound (1 N) into the compound (1 P) is carried out under the same conditions as those of the reaction of converting the compound (1 N) and the compound (10) except that the oxidizing agent is used at least in an amount of 2 moles, preferably in an amount of 2 to 4 moles, to 1 mole of the compound (1N). Reaction Scheme- 14
Figure imgf000224_0001
[wherein R1 , R2, R3a, R5, m, n, p', X, A, A-| , r and Y are the same as defined above, R6a is hydrogen atom, a lower alkyl group which may optionally have a hydroxy substituent, a phenyl-lower alkyl group which may optionally have a lower alkoxy substituent on the phenyl moiety, a furyl-lower alkyl group, or a lower alkoxy-substituted lower alkyl group, R6b is the same groups for the above mentioned R6a except hydrogen atom, R6c and R6d are each hydrogen atom or a lower alkyl group, R29 is hydrogen atom or a lower alkyl group, R30 is a lower alkyl group or a group of the formula: -A-|CONR6R7 (in which Ai , R6 and R7 are the same as defined above), R30a and R30b are each hydrogen atom or a lower alkyl group, provided that when R30 is a group of the formula: -A1CONR6R7, R29 is hydrogen atom]
The reaction of the compound (1Q) and the compound (15a) and the reaction of the compound (1S) and the compound (16a) are each carried out under the same conditions as those of the reaction of the compound (1a) and the compound (4a) in the above mentioned Reaction Scheme-2. The reaction of the compound (1Q) and the compound (15b) and the reaction of the compound (1 S) and the compound (16b) are each carried out under the same conditions as those of the reaction of the compound (1a) and the compound (4b) in the above mentioned Reaction Scheme-2.
The starting compound (2) or (3) may be prepared by the following processes. Reaction Scheme-15
Figure imgf000225_0001
(17) (3a)
[wherein R3b is the same as defined above, provided that the total number of carbon atoms of no-cyclic parts of a group of the formula: R3bCH2- in the compound (3a) is not over 6]
The reaction of converting the compound (17) into the compound (3a) is carried out by reacting the compound (17) with hydrazine in a suitable solvent or by subjecting the compound (17) to hydrolysis. The solvent used for the reaction of the compound (17) and hydrazine includes, for example, in addition to water, the same solvents for the reaction of the compound (2) and the compound (3) in the above mentioned Reaction Scheme- 1. The reaction is usually carried out at a temperature of room temperature to about 120°C, preferably at a temperature of 0 to about 100°C, for 0.5 to about 10 hours. Hydrazine is used at least in equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound (17).
The hydrolysis is carried out in the presence of an acid or a basic compound in a suitable solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.), and the like. The basic compound includes, for example, alkali metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), alkali metal or alkaline earth metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature of room temperature to about 200°C, preferably at a temperature of room temperature to about 150°C, for 10 minutes to about 25 hours. Reaction Scheme-16 - 331
R 3e. R32NH4 (19) R3e.
-C— R31 •CH
I I I
O NH2
(18) <3 >
[wherein R3 is hydrogen atom, a lower alkyl group or a lower alkenyl group, R3e is hydrogen atom, a lower alkyl group, a group of the formula: -(D)r'-R33 (D is a lower alkylene group, r' is 0 or 1 , R33 is a group of the formula:
(R5)p (R5 and p are the same as defined above), a lower alkanoyloxy -
Figure imgf000226_0001
substituted lower alkyl group, a lower alkoxy-lower alkyl group, a lower alkanoyl-substituted lower alkyl group, a lower alkoxycarbonyloxy-substituted lower alkyl group, a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring, a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same as defined above, and E is a lower alkylene group), a group of the formula:
Figure imgf000227_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above), a cycloalkyl group; naphthyl group; a group of the formula:
Figure imgf000227_0002
formula: _f~ is a 5- to 14-membered saturated or unsaturated
heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom); a phenyl group which may optionally have a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group which may optionally have a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -0-A4-CO-NR4OR41 (A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl ring; a phenyltio-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl ring; a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl ring; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl ring; a phenoxy-substituted lower alkyl group, a group of the formula: -A5-CR42R43R44 (A5, R42, R43 and R44 are the same as defined above); a 2,3-dihydro-1 H - indenyl-substituted lower alkyl group which may optionally have a substituent selected from oxo group, hydroxy group a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring; a group of the formula:
;47)u ( efined above), a group of
(R _©' R47 and u are the same as d
Figure imgf000228_0001
Figure imgf000228_0002
of the formula: a 5. χ0 14-membered unsaturated
Figure imgf000228_0003
heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 hetero - atoms selected from nitrogen atom, oxygen atom and sulfur atom), provided that wherein R3e is a phenyl group which may optionally have a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl - lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole ring, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (A4, R40 and R41 are the same as defined above), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl ring, or a group of the formula:
(R47)u, then R3 is a lower alkenyl group, and that the total number of
Figure imgf000228_0004
carbon atoms in non-cyclic part of the group of the formula: (R3e)(R31)CH- in the compound (3b) is not over 6, and R32 is a lower alkanoyloxy group]
The reaction of the compound (18) and the compound (19) is carried out under the same conditions as those of the reaction of the compound (1a) and the compound (4b) in the above Reaction Scheme-2.
The starting compound (17) is prepared by the following processes. Reaction Scheme-17
R3b-CH3
Figure imgf000229_0001
p3bι_ι
R3b-C H O R3b-COOR12
(26) (23) (25) '
[wherein R3b, R12 and X are the same as defined above, M is an alkali metal such as potassium, sodium, etc., provided that the total number of carbon atoms of non-cyclic part of the group of the formula: -CH2R3b in the compound
(17) is not over 6]
The reaction of converting the compound (20) into the compound (21) is carried out in the same manner as in the halogenation reaction of the compound (1p) in the above mentioned Reaction Scheme-7, but it is preferably carried out by adding to the reaction system a radical initiator such as 2-(4- biphenylyl)-5-phenyloxazole, azobisisobutyronitrile perbenzoic acid, etc., and a suitable amount of water (e.g. 3 mole %).
The reaction of the compound (21) and the compound (22a) is carried out under the same conditions as those of the reaction of the compound (1a) and the compound (4a) in the above Reaction Scheme-2.
The reaction of converting the compound (23) into the compound (24) is carried out under the same conditions as those of the reaction of converting the compound (1s) into the compound (1 r) in the above Reaction Scheme-8. The reaction of the compound (24) and the compound (22b) is carried out in a suitable solvent in the presence of an azodicarboxylic acid derivative such as dialkyl azodicarboxylate (e.g. diethyl azodicarboxylate, dibutyl azodicarboxylate, etc.) and a dialkylazodicarboxyamide (e.g. 1 ,1 ' - azodicarbonyldipiperidine, etc.), and a phosphorus compound such as a trialkylphosphine (e.g. trimethylphosphine, etc.) and a triarylphosphine (e.g. triphenylphosphine, etc.). The solvent may be the same solvents for the reaction of the compound (1a) and the compound (4a) in the above Reaction Scheme-2 except lower alcohols. The azodicarboxylic acid derivative, phosphorus compound and the compound (22) are each used at least in equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole of the compound (24). The reaction is usually carried out at a temperature of 0 to 100°C, preferably at a temperature of 0 to about 70°C, for 1 to about 15 hours. The reaction of converting the compound (25) into the compound (24) is carried out under the same conditions as those of the reaction of converting the compound (1s) into the compound (1 r) in the above Reaction Scheme-8.
The reaction of the compound (26) and the compound (22a) is carried out in a suitable solvent in the presence of formaldehyde and an acid. The solvent includes, for example, halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), alkanoic acids (e.g. acetic acid, propionic acid, etc.), acid anhydrides (e.g. acetic anhydride, etc.), polar solvents (e.g. acetone, dimethylformamide, etc.), or a mixture of these solvents. The acid includes, for example, inorganic acids such as hydrogen chloride gas, hydrochloric acid, hydrobromic acid, etc. Formaldehyde includes, for example, an aqueous 20 to 40 % by weight formaldehyde solution, trimer of formaldehyde, polymer of formaldehyde, i.e. para-formaldehyde, and the like. The compound (22a) is usually used at least in equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound (26). Formaldehyde is usually used at least in equimolar amount, preferably in an excess amount, to 1 mole of the compound (26). The reaction is carried out at a temperature of 0 to about 200°C, preferably at a temperature of room temperature to 150°C, for 0.5 to about 24 hours.
Reaction Scheme- 18
R3b_C N ^ R3b_c|_,2N,_|2
(27) (3c)
[wherein R3b is the same as defined above]
The reaction of converting the compound (27) into the compound (3c) is carried out under the same conditions as those of the reaction of converting the compound (1s) into the compound (1 r) in the above Reaction Scheme-8. Reaction Scheme-19 p35u
R34-A-X *► R34-A-R35 *- H2N-A-R35
(29)
(28) (30) (3d)
[wherein R34 is a group of the formula:
Figure imgf000231_0001
or a group of the formula: -NR36R37 (in which R36 and R37 are each a phenyl ■ lower alkyl group), R35 is a phenylthio group having optionally a lower alkoxy substituent on the phenyl ring, and A is the same as defined above] The reaction of the compound (28) and the compound (29) is carried out under the same conditions as those of the reaction of the compound (1 a) and the compound (4a) in the above Reaction Scheme-2.
The reaction of converting the compound (30) into the compound (3d) is carried out under the same conditions as those of the reaction of converting the compound (17) into the compound (3a) in the above Reaction
Scheme-15, when R34 of the compound (30) is a group of the formula:
Figure imgf000232_0001
When R34 of the compound (30) is a group of the formula:
-NR36R37> the reaction of converting the compound (30) into the compound (3d) is carried out under the same conditions as those of the reduction of the compound (1o) into the compound (1 m) in the above Reaction Scheme-6 wherein R14 is a phenyl-lower alkoxy group. Reaction Scheme-20
Figure imgf000232_0002
(33d) (33c) (33b) [wherein R1, R2, R12 and r are the same as defined above]
The reaction of the compound (31 ) and the compound (32) is carried out in the presence of a basic compound. The basic compound includes the same basic compounds as used for the reaction of the compound (1a) and the compound (4a) in the above Reaction Scheme-2. The compound
(32) is used at least in equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound (31). The reaction is carried out at a temperature of 0 to 100°C, preferably at a temperature of 0 to about 70°C, for 1 hour to about 5 day. The reaction of converting the compound (33a) into the compound (33b) is carried out in the presence of a halogenated phosphorus compound such as phosphorus tribromide, phosphorus trichloride, etc. in a suitable solvent. The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. chloroform, methylene chloride, carbon tetrachloride, etc.), and the like. The halogenated phosphorus compound is used in an amount of 1 to 2 moles, to 1 mole of the compound (33a). The reaction is usually carried out at a temperature of 0 to 100°C, preferably at a temperature of 0 to about 70°C, for 0.5 to 5 hours.
The reaction of converting the compound (33a) into the compound (33c) is carried out by reacting the compound (33a) with sodium hydrosulfate in the presence of an acid in a suitable solvent. The solvent includes, for example, alcohols (e.g. methanol, ethanol, propanol, butanol, 3 - methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), water, and the like. The acid includes, for example, mineral acids such as hydrochloric acid, etc. Sodium hydrosulfate is used at least in equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound (33a). The reaction is usually carried out at a temperature of 0 to 100°C, preferably at a temperature of 0 to about 70°C, for 1 to about 10 hours.
The reaction of converting the compound (33c) into the compound (33d) is carried out under the same conditions as those of the reaction of converting the compound (1c) into the compound (1d) in the above Reaction Scheme-3. The reaction of converting the compound (33a) into the compound (33d) is carried out under the same conditions as those of the above mentioned reaction of converting the compound (33a) into the compound (33d) except a trialkylphosphite such as trimethylphosphite is used instead of a halogenated phosphorus compound, and the solvent used therein may be an alcohol such as 1 -propanol, etc., and the reaction is carried out at a temperature of 0 to 150°C, preferably at a temperature of 0 to 100°C. Reaction Scheme-21
Figure imgf000234_0001
03) (2)
[wherein R , R2, R"-2, r, m and n are the same as defined above]
The hydrolysis of the compound (33) is carried out under the same conditions as those of the hydrolysis of the compound (1j) in the above Reaction Scheme-5. The esterification of the compound (2) is carried out by reacting the starting compound with an alcohol (e.g. methanol, ethanol, isopropanol, etc.) in the presence of an inorganic acid (e.g. hydrochloric acid, sulfuric acid, etc.) and a halogenating agent such as thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, etc., at a temperature of 0 to 150°C, preferably at a temperature of 50 to 100°C, for 5 minutes to about 10 hours.
The intermediate compound (24a) is prepared by the following Reaction Scheme-22. Reaction Scheme-22
Figure imgf000235_0001
(20b)
(R8)α' (R8) q'
Figure imgf000235_0002
(20c) (24a)
[wherein R8, q' and R12 are the same as defined above] The reaction of converting the compound (20a) into the compound (20b) is carried out in the presence of an oxidizing agent in a suitable solvent. The solvent and the oxidizing agent used therein are the same solvents and oxidizing agents as used for the reaction of the converting the compound (1c) into the compound (1d) in the above Reaction Scheme-3, respectively. The oxidizing agent is usually used in an excess amount to the compound (20a). The reaction is usually carried out at a temperature of room temperature to 150°C, preferably at a temperature of room temperature to about 120°C, for 1 to about 20 hours.
The reaction of converting the compound (20b) into the compound (20c) is carried out by heating the compound (20b) in the presence of a compound of the formula: R12C00C0R12 (R12 is the same as defined above) at a temperature of room temperature to about 200°C, preferably at a temperature of room temperature to 150°C, for 1 to 10 hours.
The reaction of converting the compound (20c) into the compound (24a) is carried out under the same conditions as those of the hydrolysis of the compound (1j) in the above Reaction Scheme-5.
The compound (1 ) wherein R5 or R8 is an amino group is prepared by reducing the corresponding compound (1) wherein R5 or R8 is nitro group.
The reduction reaction is carried out, for example, (a) by using a catalyst in a suitable solvent, or (b) by using as a reducing agent a mixture of a metal or a metal salt with an acid, a mixture of a metal or a metal salt and an alkali metal hydroxide, an alkali metal sulfite or an alkali metal ammonium salt in an inert solvent.
When the above (a) is employed, the solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. N,N - dimethylformamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney-nickel, and the like. The catalyst is used in an amount of 0.02 to 1 mole, to 1 mole of the starting compound. The reaction is carried out at a temperature of -20 to 150°C, preferably, at a temperature of 0 to 100°C, under 1 to 10 atms of hydrogen gas, for 0.5 to 10 hours. An acid (e.g. hydrochloric acid) may be added to the reaction system. When the method (b) is employed, there is used as a reducing agent a mixture of iron, zinc, tin or stannous chloride and a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or a mixture of iron, iron sulfide, zinc or tin and an alkali metal hydroxide (e.g. sodium hydroxide, etc.), sulfide (e.g. ammonium sulfide, etc.), aqueous ammonia, ammonium salt (e.g. ammonium chloride, etc.). The inert solvent includes, for example, water, methanol, ethanol, dioxane, acetic acid, and the like. The conditions for reduction can be selected according to the kinds of the reducing agent to be used. For example, when a mixture of stannous chloride and hydrochloric acid is used as a reducing agent, the reaction is preferably carried out at a temperature from 0°C to about room temperature, for 0.5 to about 10 hours. The reducing agent may be used at least in equimolar amount, usually in an amount of 1 mole to 5 moles, to 1 mole of the starting compound. Reaction Scheme-23
Figure imgf000237_0001
(1X)
[wherein R1 , R2, R3a, R8, R39, m, n, q', D, r, r' and the group of the formula: are the same as defined above, R48 is a lower alkoxy group, R49 is a
-© lower alkoxycarbonyl group, and R50 and R51 are the same or different and each hydrogen atom or a lower alkyl group]
The reaction of the compound (1 U) and the compound (34) is carried out in the presence of a basic compound in a suitable solvent. The basic compound includes, for example, inorganic bases (e.g. metal sodium, metal potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc.), organic bases such as an alkali metal alcoholate (e.g. sodium methylate, sodium ethylate, potassium t-butoxide, etc.), an alkyl lithium, aryl lithium or lithium amide (e.g. methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropylamide, etc.), pyridine, piperidine, quinoline, triethylamine, N,N-dimethylaniline, and the like. The solvent may be any one which does hot affect the reaction, and includes, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethyl sulfoxide, hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), and the like. The reaction is usually carried out at a temperature from -80°C to 150°C, preferably at a temperature from -80 to about 120°C, for 0.5 to about 15 hours.
The reaction of converting the compound (1V) into the compound (1 W) can be carried out under the same conditions as those of the hydrolysis of the compound (1j) in the above Reaction Scheme-5. The reaction of the compound (1W) and the compound (35) can be carried out under the same conditions as those of the reaction of the compound (2) and the compound (3) in the above Reaction Scheme-1. Reaction Scheme-24
Figure imgf000238_0001
(1a) (1Y)
[wherein R1 , R2, m, n, r and R3a are the same as defined above, R3c' is a phenyl - lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a phenoxycarbonyl group, or a group of the formula: -CO-A-NR52R53 (in which A, R52, R53 are the same as defined above)]
The reaction of the compound (1a) and the compound (38) is carried out under the same conditions as those of the reaction of the compound (2) and the compound (3) in Reaction Scheme- 1. In said reaction, when the compound (38) is used in the form of an acid anhydride, the reaction of the carboxylic acid anhydride and the amine compound is carried out in the same manner as in the reaction of the compound (2) and the compound (3) when the active ester method is employed, i.e. in the presence of a basic compound in a solvent at a temperature of 0 to 150°C, preferably at a temperature of 10 to
100°C, for 5 to 30 hours. The carboxylic acid anhydride compound is used at least in equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound (1a).
The compound (1 ) wherein R8 is a lower alkanoyl group is prepared by reacting the corresponding compound (1 ) wherein R8 is cyano group with a compound of the formula: Ri?MgX (11 ) (wherein Ri 7 and X are the same as defined above), followed by subjecting the resultant to hydrolysis. The reaction of the compound (1 ) and the compound (11) is carried out under the same conditions as those of the reaction of the compound (1s) and the compound (11) in the above Reaction Scheme-8. The subsequent hydrolysis is carried out under the same conditions as those of the hydrolysis of the compound (1j) in the above Reaction Scheme-5. The reaction is preferably carried out in the presence of an acid.
The compound (1) wherein R5 is a 1 ,3-dioxolanyl group having optionally a lower alkyl substituent or R8 is a 1 ,3-dioxolanyl-substituted lower alkyl group having optionally a lower alkyl substituent is prepared by reacting the corresponding compound (1 ) wherein R5 is a lower alkanoyl group or R8 is a lower alkanoyl-substituted lower alkyl group with a compound of the formula:
(wherein R38 is a lower alkyl group, v is 0 or an integer of 1 to 3). The reaction is carried out in the presence of an acid in a suitable solvent. The solvent includes, for example, in addition to the same solvents for the above mentioned reaction of the compound (1a) and the compound (4a) in the above mentioned Reaction Scheme-2, halogenated hydrocarbons (e.g. methylene chloride, dichloroethane, chloroform, etc.). The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. p-toluenesulfonic acid, etc.), and the like. The compound (36) is used at least in equimolar amount, preferably in an amount of 1 to 10 mole, to 1 mole of the starting compound. The reaction is usually carried out at a temperature of room temperature to 150°C, preferably at a temperature of room temperature to about 100°C, for 1 to about 24 hours.
The compound (1) wherein R5 is a lower alkanoyl group or R8 is a lower alkanoyl-substituted lower alkyl group is prepared by hydrolysis of the corresponding compound (1 ) wherein R5 is a 1 ,3-dioxolanyl group having optionally a lower alkyl substituent, or R8 is a 1 ,3-dioxolanyl-substituted lower alkyl group having optionally a lower alkyl substituent. The hydrolysis is carried out in the presence of an acid in a suitable solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), or a mixture of these solvents. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organic acids (e.g. p-toluenesulfonic acid, etc.). The reaction is carried out at a temperature of 0 to 70°C, preferably at a temperature of 0°C to room temperature, for 1 to 10 about hours.
The compound (1) wherein R8 is a tetrazolyl group having a substituent selected from a lower alkyl group and a lower alkoxy-lower alkyl group is prepared by reacting the corresponding compound (1) wherein R8 is a tetrazolyl group with a compound of the formula: R39X (37) (wherein R39 is a lower alkyl group or a lower alkoxy-lower alkyl group, and X is the same as defined above) in the same manner as in the reaction of the compound (10) with the compound (4a) in the above mentioned Reaction Scheme-2.
The compound (1) wherein R8 is unsubstituted tetrazolyl group is prepared by subjecting the compound (1) wherein R8 is a tetrazolyl group having a lower alkoxy-lower alkyl substituent, to hydrolysis in the same manner as in the hydrolysis of the compound (1o) wherein R14 is a lower alkoxy - substituted lower alkoxy group in the above mentioned Reaction Scheme-6.
The compound (1) wherein R2 is a morpholino-substituted lower alkyl group or an imidazolyl-substituted lower alkyl group is prepared by reacting the corresponding compound (1) wherein R2 is a lower alkyl group having a halogen substituent with morpholine or imidazole in the same manner as in the reaction of the compound (1a) and the compound (4a) in the above mentioned Reaction Scheme-2.
The compound (1) wherein R2 is a halogen-substituted methyl group is prepared by reacting the corresponding compound (1) wherein R2 is methyl group in the same manner as in the reaction of converting the compound (20) into the compound (21) in the above mentioned Reaction
Scheme-17. Further, the compound (1) wherein R2 is a halogen-substituted methyl group (in which halogen atom is fluorine atom ) is also prepared by reacting the corresponding compound (1) wherein R2 is a halogen-substituted methyl group (in which halogen atom is other than fluorine atom) with silver fluoride.
Among the desired compounds (1) of the present invention, the compounds having a basic group can easily be converted into acid addition salts thereof by treating them with a pharmaceutically acceptable acid. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, etc.), and organic acids (e.g. oxalic acid, acetic acid, succinic acid, malonic acid, methanesulfonic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, etc.). These salts show as well excellent antidiabetic activity as the free compounds (1). Besides, among the desired compounds (1) of the present invention, the compounds having an acidic group can easily be converted into salts by treating them with a pharmaceutically acceptable basic compound. The basic compound includes, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium hydrogen carbonate, and the like. The desired compound of each process can easily be isolated and purified by conventional isolation methods. The isolation methods are, for example, extraction with solvent, dilution method, recrystallization method, column chromatography, preparative thin layer chromatography, and the like. In addition, the compounds (1 ) of the present invention include stereoisomers and optical isomers, and these isomers are also useful as antidiabetic agents.
The desired compounds (1 ) of the present invention and salts thereof are useful as antidiabetic agent and are used in the form of a conventional pharmaceutical preparation. The preparation is prepared by using conventional diluents or carriers such as fillers, thickening agents, binders, wetting agent, disintegrators, surfactants, lubricants, and the like. The pharmaceutical preparations can be selected from various forms in accordance with the desired utilities, and the representative forms are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.), and the like. In order to form in tablets, there are used carriers such as vehicles (e.g. lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc.), binders (e.g. water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinyl - pyrrolidone, etc.), disintegrators (e.g. dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose, etc.), disintegration inhibitors (e.g. white sugar, stearin, cacao butter, hydrogenated oils, etc.), absorption promoters (e.g. quaternary ammonium base, sodium laurylsulfate, etc.), wetting agents (e.g. glycerin, starches, etc.), adsorbents (e.g. starches, lactose, kaolin, bentonite, colloidal silicates, etc.), lubricants (e.g. purified talc, stearates, boric acid powder, polyethylene glycol, etc.), and the like. Moreover, the tablets may also be in the form of a conventional coated tablet, such as sugar-coated tablets, gelatin-coated tablets, enteric coated tablets, film coating tablets, or double or multiple layer tablets. In the preparation of pills, the carriers may be conventional ones, and include, for example, vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc, etc.), binders (e.g. gum arabic powder, tragacanth powder, gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.), and the like. In the preparation of suppositories, the carriers may be conventional ones, and include, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin, semi-synthetic glycerides, and the like. Capsules can be prepared by charging a mixture of the compound of the present invention and the above carriers into hard gelatin capsules or soft capsules in usual manner. In the preparation of injections, the solutions, emulsions and suspensions are sterilized and are preferably made isotonic with the blood. In the preparation of these solutions, emulsions and suspensions, there are used conventional diluents, such as water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, the pharmaceutical preparations may also be incorporated with sodium chloride, glucose, or glycerin in an amount sufficient to make them isotonic, and may also be incorporated with conventional solubilizers, buffers, anesthetizing agents. Besides, the pharmaceutical preparations may optionally be incorporated with coloring agent, preservatives, perfumes, flavors, sweetening agents, and other medicaments, if required.
The amount of the desired compound of the present invention to be incorporated into the pharmaceutical preparation is not specified but may be selected from a broad range, but usually, it is preferably in the range of 1 to 70 % by weight. The pharmaceutical preparation of the present invention containing as an active ingredient the compounds (1 ) of the present invention or a salt thereof may be administered in any method, and suitable method for administration may be determined in accordance with various forms of preparations, ages, sexes and other conditions of the patients, the degree of severity of diseases, and the like. For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. The injections are intravenously administered alone or together with a conventional auxiliary liquid (e.g. glucose, amino acid solutions), and further are optionally administered alone in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route, if required. Suppositories are administered in intrarectal route.
The dosage of the pharmaceutical preparation of the present invention may be selected in accordance with the usage, ages, sexes and other conditions of the patients, the degree of severity of the diseases, and the like, but it is usually in the range of about 0.2 to 200 mg of the active compound of the present invention per 1 kg of body weight of the patient per day.
Best Mode for Carrying Out the Invention
Examples
The present invention is illustrated in more detail by the following Preparations of antidiabetic agent, Reference Examples of processes for preparing the starting compounds to be used for preparing the desired compounds of the present invention, and Examples of processes for preparing the desired compounds, and Experiments of the activities of the desired compounds of the present invention.
Preparation 1 Tablets are prepared from the following components.
Components Amount
2-(2-Benzofuranylmethylaminocarbonyl)- 3-methylquinoxalin-4-oxide 5 mg
Starch 132 mg Magnesium stearate 18 mg
Lactose 45 mg
Totally 200 mg
In the conventional manner, these are obtained tablets each containing the above components. Preparation 2
Film coated tablets are prepared from the following components.
Components Amount
2-[3-(4-Methoxyphenyl)propylaminocarbonyl]- 3-methylquinoxalin-4-oxide 150 mg Avicel (trade name of microcrystalline cellulose manufactured by Asahi Chemical Industry, Co., Ltd. Japan) 40 g
Corn starch 30 g
Magnesium stearate 2 g Hydroxypropyl methylcellulose 10 g
Polyethylene glycol-6000 3 g
Castor oil 40 g
Methanol 40 g
The active compound of the present invention, Avicel, corn starch and magnesium stearate are mixed and kneaded and the mixture is tabletted using a conventional pounder (R 10 mm) for sugar coating. The tablets thus obtained are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil and methanol to give film coated tablets. Reference Example 1
A solution of 2-ethoxycarbonyl-3-methylbenzofuran (5.0 g) in anhydrous diethyl ether (10 ml) is added dropwise to a suspension of lithium aluminum hydride (0.93 g) in diethyl ether (30 ml) under ice-cooling, and the mixture is stirred at room temperature for 30 minutes. The mixture is cooled, and decomposed with saturated aqueous sodium sulfate solution. The mixture is filtered through celite, and dried over anhydrous sodium sulfate, and the residue is evaporated to remove the solvent to give 2-hydroxymethyl-3 - methylbenzofuran (3.7 g) as white powder.
1H-NMR (CDCI3) δ ppm: 1.82 (1 H, t, J=6 Hz), 2.27 (3H, s), 4.76 (2H, d, J=6 Hz), 7.20-7.55 (4H, m)
Reference Example 2
In tetrahydrofuran (40 ml) are suspended 2-hydroxymethyl-3 - methylbenzofuran (3.7 g), triphenylphosphine (6.6 g) and phthalimide (3.7 g), and thereto is added dropwise a solution of diethyl azodicarboxylate (4.4 g) in tetrahydrofuran (10 ml) under ice-cooling. The mixture is stirred at room temperature overnight, and evaporated to remove the solvent, and the resulting residue is purified by silica gel column chromatography (solvent; methylene chloride), and crystallized from diethyl ether. The crystals are collected by filtration, and dried to give 3-methyl-2-phthalimidomethylbenzofuran (4.6 g) as white powder.
1H-NMR (CDCI3) δ ppm: 2.40 (3H, s), 4.97 (2H, s), 7.10-7.30 (2H, m),
7.40 (1 H, d, J=7 Hz), 7.48 (1 H, d, J=7 Hz), 7.65-7.75 (2H, m), 7.80-7.90 (2H, m) Reference Example 3
To methanol (80 ml) is added 3-methyl-2-phthalimidomethyl - benzofuran (4.6 g), and thereto is added hydrazine hydrate (1.2 g), and the mixture is refluxed for three hours. The mixture is evaporated to remove the solvent, and to the residue is added diluted aqueous sodium hydroxide solution, and then the mixture is extracted with chloroform. The chloroform layer is washed with saturated brine solution, and dried over anhydrous sodium sulfate. The residue is evaporated to remove the solvent to give 2 - aminomethyl-3-methylbenzofuran (3.0 g) as colorless transparent liquid.
1H-NMR (CDCI3) δ ppm: 1.55 (2H, brs), 2.21 (3H, s), 3.93 (2H, s), 7.15 - 7.30 (2H, m), 7.35-7.50 (2H, m)
Reference Example 4
To carbon tetrachloride (50 ml) are added 2-methylbenzo - thiophene (4.0 g), N-bromosuccinimide (4.8 g) and azobisisobutyronitrile (0.3 g), and the mixture is refluxed for five hours. After cooling, the insoluble materials are removed by filtration, and the filtrate is concentrated to give 2 - bromomethylbenzothiophene (6.7 g) as brown powder.
1H-NMR (CDCI3) δ ppm: 4.79 (2H, s), 7.30-7.45 (2H, m), 7.36 (1 H, s),
7.70-7.85 (2H, m)
Reference Example 5 In dimethylformamide (40 ml) is dissolved 2-bromomethyl - benzothiophene (6.7 g), and thereto is added potassium phthalimide (5.0 g), and the mixture is stirred at 60°C for two hours. The mixture is evaporated to remove the dimethylformamide, and the residue is extracted with chloroform. The extract is washed with water and saturated brine solution, dried over anhydrous sodium sulfate, and evaporated to remove the solvent. To the residue is added diethyl ether, and the precipitated crystals are collected by filtration, and dried to give 2-phthalimidomethylbenzothiophene (4.5 g) as pale brown powder.
1H-NMR (CDCI3) δ ppm: 5.10 (2H, s), 7.20-7.40 (3H, m), 7.70-7.80 (4H, m), 7.80-7.95 (2H, m)
Reference Example 6
3-Formylbenzofuran (4.3 g) is dissolved in methanol (50 ml), and thereto is added gradually sodium borohydride (1.1 g) under ice-cooling. The mixture is stirred at the same temperature for one hour, and evaporated to remove the methanol. The residue is extracted with chloroform, and the extract is washed with water, and dried over anhydrous sodium sulfate. The residue is evaporated to remove the solvent to give 3-hydroxymethylbenzofuran (4.1 g) as pale yellow liquid.
1H-NMR (CDCI3) δ ppm: 1.62 (1 H, t, J=5 Hz), 4.85 (2H, d, J=5 Hz), 7.20 -
7.45 (2H, m), 7.53 (1 H, d, J=8 Hz), 7.62 (1 H, s), 7.68 (1 H, d, J=8 Hz) Reference Example 7 A solution of ethyl 2-benzofuranacrylate (3.46 g) in dry toluene is cooled to -50°C, and thereto is added dropwise alminum diisobutyl hydride (1 M toluene solution, 37 ml). The mixture is stirred at -20°C for one hour, and thereto is added methanol (30 ml), and the mixture is stirred at room temperature overnight. The precipitates are removed by filtration, and the filtrate is concentrated. The residue is dissolved in ethyl acetate, and filtered through Florisil (an activated magnesium silicate), and concentrated to give 2 - (3-hydroxy-1-propenyl)benzofuran (2.6 g) as colorless liquid.
1H-NMR (CDCI3) δ ppm: 4.39 (2H, brs), 6.60 (3H, m), 7.17-7.32 (2H, m), 7.43 (1H, d, J=7 Hz), 7.52 (1H, d, J=7 Hz) Reference Example 8
Into a mixture of benzothiophene (13.4 g) and 37 % aqueous formaldehyde solution (15 ml) is blown hydrogen chloride gas for about 20 to 30 minutes under ice-cooling. The mixture is stirred at room temperature for two hours. The reaction mixture is poured into ice-water, and extracted with diethyl ether. The extract is washed with saturated sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the resulting residue and potassium phthalimide (18.5 g) are dissolved in diemthylformamide (100 ml). The mixture is heated at 60°C for 1.5 hour, and after cooling, the mixture is poured into ice-water. The precipitated crystals are collected by filtration, washed with diisopropyl ether to give 3-phthalimidomethylbenzothiophene (13.4 g) as pale brown crystals.
1H-NMR (CDCI3) δ ppm: 5.08 (2H, s), 7.3-7.5 (2H, m), 7.61 (1 H, s), 7.6 - 7.9 (5H, m), 8.15 (1 H, d, J=8 Hz)
Reference Example 9 2-Acetylbenzofuran (3.2 g) is dissolved in methanol (60 ml), and thereto are added ammonium acetate (15 g) and sodium cyanoborohydride (1.26 g). The mixture is stirred at room temperature overnight, and thereto is added diluted aqueous hydrochloric acid solution to make the solution acidic. The mixture is washed with ethyl acetate, and the aqueous layer is basified with aqueous sodium hydroxide solution, and extracted with chloroform. The chloroform layer is washed with water, dried over anhydrous sodium sulfate, and evaporated to remove chloroform to give 2-(1-aminoethyl)benzofuran (1.8 g) as colorless liquid.
1H-NMR (CDCI3) δ ppm: 1.52 (3H, d, J=6 Hz), 1.83 (2H, brs), 4.20 (1 H, q, J=6 Hz), 6.50 (1 H, s), 7.15-7.30 (2H, m), 7.43 (1 H, d, J=8 Hz), 7.51 (1 H, d, J=8 Hz) Reference Example 10
5-Ethyl-2-methylpyridine (25 g) is dissolved in acetic acid (200 ml), and thereto is added 30 % aqueous hydrogen peroxide solution (25 ml), and the mixture is heated at 100°C. Four hours later, to the mixture is added 30 % aqueous hydrogen peroxide solution (25 m), and the mixture is heated with stirring at the same temperature for 14 hours. After cooling, the mixture is concentrated several times with adding water thereto. The final residue is neutralized with saturated aqueous potassium carbonate solution, and extracted with chloroform. The extract is dried over anhydrous potassium carbonate, and evaporated to remove the solvent. The resulting residue is dissolved in acetic anhydride (200 ml), and the mixture is heated at 120°C for 4 hours. The mixture is evaporated to remove the solvent, and thereto is added saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract is dried over anhydrous sodium sulfate, and evaporated to remove the solvent. The residue is dissolved in methanol (200 ml), and thereto is added potassium carbonate (57 g), and the mixture is stirred at room temperature for 12 hours. The mixture is evaporated to remove the solvent, and thereto is added water. The mixture is extracted with chloroform, and dried over anhydrous potassium carbonate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; ethyl acetate : n-hexane=1 : 4) to give 5-ethyl-2 - hydromethylpyridine (20.4 g) as pale brown liquid.
1H-NMR (CDCI3) δ ppm: 1.26 (3H, t, J=8 Hz), 2.66 (2H, q, J=8 Hz), 3.67 (1 H, br), 4.73 (2H, s), 7.18 (1 H, d, J=8 Hz), 7.52 (1 H, d, J=8 Hz), 8.41 (1 H, s) Reference Example 11
4-(2-Methyl-1 ,3-dioxolan-2-yl)benzonitrile (1.9 g) is dissolved in diethyl ether (20 ml), and thereto is added lithium aluminum hydride (400 mg) at 0°C. The mixture is reacted at room temperature for 14 hours, and thereto are added water (1 ml) and 8M aqueous sodium hydroxide solution (3 ml). To the mixture is added magnesium sulfate, and the insoluble materials are removed by filtration. The filtrate is concentrated to give [4-(2-methyl-1 ,3 - dioxolan-2-yl)benzyl]amine (2.1 g) as colorless oil.
1H-NMR (CDCI3) δ ppm: 7.45 (2H, d, J=8 Hz), 7.29 (2H, d, J=8 Hz), 4.04 (2H, m), 3.87 (2H, s), 3.77 (2H, m), 1.77 (2H, br), 1.65 (3H, s)
Reference Example 12
N-Bromoethylphthalimide (13 g) and p-methoxythiophenol (7.9 g) are dissolved in dimethylformamide (70 ml), and thereto is added potassium carbonate (10 g). The mixture is stirred at 70°C overnight, and evaporated to remove the solvent. The residue is extracted with diethyl ether, washed with water, and dried over anhydrous sodium sulfate. The residue is evaporated to remove diethyl ether, and crystallized from n-hexane. The crystals are collected by filtration, and dried to give N-[2-(4-methoxyphenylthio)ethyl] - phthalimide (13.9 g) as white powder. 1H-NMR (CDCI3) δ ppm: 3.14 (2H, t, J=7 Hz), 3.75 (3H, s), 3.89 (2H, t,
J=7 Hz), 6.80 (2H, d, J=8 Hz), 7.42 (2H, d, J=8 Hz), 7.65-7.75 (2H, m), 7.75-7.90 (2H, m)
Reference Example 13
N-(2-Chloroethyl)dibenzylamine • hydrochloride (25 g) and phenol (8.0 g) are dissolved in dimethylformamide (100 ml), and thereto is added potassium carbonate (30 g). The mixture is stirred at 70°C for 6 hours, and evaporated to remove dimethylformamide. The residue is extracted with diethyl ether, and the extract is washed with water, and dried over anhydrous sodium sulfate. The residue is evaporated to remove diethyl ether to give N-(2 - phenoxyethyl)dibenzylamine (25.5 g) as colorless oil.
1H-NMR (CDCI3) δ ppm: 2.90 (2H, t, J=6 Hz), 3.72 (4H, s), 4.03 (2H, t, J=6 Hz), 6.80 (2H, d, J=8 Hz), 6.85-7.00 (1 H, m), 7.15-7.45 (12H, m) Reference Example 14
N-(2-Phenoxyethyl)dibenzylamine (25.5 g) is dissolved in ethanol (500 ml), and thereto is added 10 % palladium-carbon (3.0 g). The mixture is subjected to hydrogenation at 50°C under 1 atm of hydrogen gas. The catalyst is removed by filtration, and the filtrate is evaporated to remove ethanol to give 2-phenoxyethylamine (11.0 g) as colorless oil.
1H-NMR (CDCI3) δ ppm: 1.47 (2H, brs), 3.08 (2H, t, J=5 Hz), 4.01 (2H, t, J=5 Hz), 6.85-7.00 (3H, m), 7.25-7.35 (2H, m) Reference Example 15 To triethylamine (1.5 liter) are added benzofuroxane (216 g) and ethyl acetoacetate (207 g), and the mixture is stirred at room temperature for four days. The precipitated crystals are collected by filtration, washed with water, dried, and crystallized from ethyl acetate to give 2-ethoxycarbonyl-3 - methylquinoxaline-1 ,4-dioxide (115 g) as pale yellow needles. M.p. 137-138°C
Reference Example 16
2-Ethoxycarbonyl-3-methylquinoxaline-1 ,4-dioxide (77 g) is dissolved in ethanol (3.5 liters) and cone, hydrochloric acid (200 ml), and to the mixture is added dropwise aqueous solution of sodium hydrosulfite (200 g) in water (1 liter) with stirring at room temperature. The mixture is stirred at the same temperature for four hours, and the reaction mixture is neutralized with sodium hydrogen carbonate, and evaporated to remove ethanol. To the residue is added water, and the precipitated crystals are collected by filtration, washed with water, dried, and recrystallized from n-pentane to give 2-ethoxy - carbonyl-3-methylquinoxaline (67 g) as colorless needles. M.p. 74-75°C
Reference Example 17
2-Ethoxycarbonyl-3-methylquinoxaline (64 g) is dissolved in methylene chloride (700 ml), and thereto is added gradually m-chloro - perbenzoic acid (70 g) under ice-cooling. The mixture is stirred at room temperature overnight, and the reaction solution is washed successively with diluted aqueous sodium thiosulfate solution, saturated sodium hydrogen carbonate solution, and water, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and to the residue is added n - hexane. The precipitated crystals are collected by filtration, dried, and recrystallized from n-hexane/diethyl ether to give 2-ethoxycarbonyl-3 - methylquinoxalin-4-oxide (45 g) as colorless needles. M.p. 91 -93°C
Reference Example 18
2-Ethoxycarbonyl-3-methylquinoxaline-1 ,4-dioxide (105 g) is dissolved in chloroform (500 ml), and thereto is added dropwise gradually phosphorus tribromide (44 ml) under ice-cooling. The mixture is stirred at room temperature for one hour, and evaporated to remove the solvent. The residue is poured into ice-water, and neutralized with potassium carbonate. The mixture is extracted with chloroform, washed with water, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; n - hexane : ethyl acetate = 2 : 1), and recrystallized from ethyl acetate/n-hexane to give 2-ethoxycarbonyl-3-methylquinoxalin-1 -oxide (35 g) as colorless prisms. M.p. 85-87°C
Reference Example 19
2-Ethoxycarbonyl-3-methylquinoxalin-4-oxide (4.0 g) is suspended in methanol (80 ml) and 5N aqueous sodium hydroxide solution (10 ml), and the mixture is stirred at room temperature for three hours. The mixture is evaporated to remove the solvent, and the residue is dissolved in water. The aqueous layer is washed with ethyl acetate, and acidified with hydrochloric acid. The precipitated crystals are collected by filtration, washed with water, and dried to give 2-carboxy-3-methylquinoxaline-4-oxide (3.2 g) as white powder.
M.p. 143-145°C (decomposed) Reference Example 20
2-Carboxyquinoxaline (2.0 g) is dissolved in methanol (20 ml), and thereto is added dropwise thionyl chloride (1.3 ml) under ice-cooling. The mixture is refluxed for 15 minutes, and evaporated to remove the solvent. The residue is extracted with chloroform, and the extract is washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. The residue is evaporated to remove the solvent, and the resulting 2-methoxycarbonylquinoxaline is dissolved in methylene chloride (40 ml). To the mixture is added m-chloroperbenzoic acid (2.9 g) with stirring at room temperature, and the mixture is stirred at room temperature overnight. The reaction solution is washed with diluted aqueous sodium thiosulfate solution and saturated sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and to the residue is added n-hexane. The precipitated crystals are collected by filtration, and dried to give 2-methoxycarbonylquinoxalin-4-oxide (2.0 g) as yellow powder.
M.p. 154-155°C
Reference Example 21
2-Ethoxycarbonyl-3-methylquinoxaline (2.2. g) is dissolved in carbon tetrachloride (40 ml), and thereto are added N-bromosuccinimide (2.7 g) and perbenzoic acid (0.2 g), and the mixture is refluxed for 8 hours. The mixture is evaporated to remove the solvent, and thereto is added water. The mixture is extracted with dichloromethane, and the extract is dried over anhydrous sodium sulfate, and evaporated. The residue is dissolved in isopropanol (50 ml), and thereto is added imidazole (2.8 g). The mixture is refluxed for 10 hours, and evaporated to remove the solvent. To the residue is added water, and the mixture is extracted with chloroform, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane : methanol = 16 : 1 ) to give 2-ethoxycarbonyl-3-(1 - imidazolyl)methylquinoxaline (1.33 g) as yellow powder.
1H-NMR (CDCI3) δ ppm: 1.47 (3H, t, J=7 Hz), 4.55 (2H, q, J=7 Hz), 5.82
(2H, s), 7.04 (2H, d, J=5 Hz), 7.70 (1 H, s), 7.8-8.0 (2H, m), 8.0-8.1 (1 H, m), 8.2 - 8.3 (1 H, m)
By using the suitable starting compounds, there are obtained the following compounds as listed in Table 1 in the same manner as in Reference Examples 3, 9, 11 and 14. Table 1
Figure imgf000254_0001
Figure imgf000255_0001
Figure imgf000256_0001
Figure imgf000257_0001
Figure imgf000258_0001
Figure imgf000259_0001
Figure imgf000260_0001
Figure imgf000261_0001
Figure imgf000262_0001
Figure imgf000263_0001
Figure imgf000264_0001
Figure imgf000265_0001
Figure imgf000266_0001
Figure imgf000267_0001
Using suitable starting compounds, there are obtained the compounds as listed in Table 2 in the same manner as in Reference Examples 15-21.
Table 2
Figure imgf000268_0001
Figure imgf000269_0001
Figure imgf000270_0001
Figure imgf000271_0001
Figure imgf000272_0001
Using the suitable starting compounds, there are obtained the compounds as listed in Table 3 in the same manner as in Reference Example 3, 9, 11 adn 14.
Table 3
Figure imgf000272_0002
Figure imgf000273_0001
Figure imgf000274_0001
Figure imgf000275_0001
Figure imgf000276_0001
Figure imgf000277_0001
Figure imgf000278_0001
Figure imgf000279_0001
Figure imgf000280_0001
Figure imgf000281_0001
Figure imgf000282_0001
Figure imgf000283_0001
Figure imgf000284_0001
Figure imgf000285_0001
Figure imgf000286_0001
Figure imgf000287_0001
Figure imgf000288_0001
Figure imgf000289_0001
Figure imgf000290_0001
Figure imgf000291_0001
Figure imgf000292_0001
Figure imgf000293_0001
Figure imgf000294_0001
compounds as listed in Table 4 in the same manner as in Reference Examples 15-21.
Table 4
Figure imgf000294_0002
Figure imgf000295_0001
*: 1H-NMR(CDCI3)ppm:
1.53 (3H, t, J=7 Hz), 4.61 (2H, d, J=7 Hz), 5.14 (2H, s), 7.81-7.93 (2H, m), 8.11 (1H, m), 8.23(1 H,m)
Example 1
2-Ethoxycarbonyl-3-methylquinoxalin-4-oxide (1.5 g) is mixed with 3-aminomethylbenzofuran (1.9 g) under nitrogen atmosphere, and the mixture is stirred at 60°C overnight. The reaction mixture is purified by silica gel column chromatography (solvent; n-hexane : ethyl acetate = 3 : 1), and recrystallized from ethanol to give 2-[(3-benzofuranyl)methylaminocarbonyl]-3 - methylquinoxalin-4-oxide (1.3 g) as colorless needles. M.p. 143-144°C Example 2 2-Carboxy-3-methylquinoxalin-4-oxide (0.8 g) and 2-aminomethyl
5-dimethyiaminobenzofuran (0.9 g) are dissolved in dimethylformamide (10 ml), and thereto are added dropwise successively diethyl cyanophosphate (0.8 g) and triethylamine (0.8 g) under ice-cooling. The mixture is stirred at room temperature overnight, extracted with ethyl acetate, and washed with water. The mixture is dried over anhydrous sodium sulfate, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; n-hexane : ethyl acetate = 1 : 1), and recrystallized from acetonitrile to give 2-[(5-dimethylamino-2-benzofuranyl)methylaminocarbonyl]-3 - methylquinoxalin-4-oxide (0.6 g) as yellow plates. M.p. 155-157°C
Example 3
2-Quinoxalinecarboxylic acid (0.5 g) is dissolved in dichloromethane (10 ml), and thereto is added dicyclohexylcarbodiimide (0.7 g). The mixture is stirred for 30 minutes, and thereto is added 2 - aminomethylbenzofuran (0.5 g), and the mixture is stirred overnight. The insoluble materials are removed by filtration, and the organic layer is washed , with saturated sodium hydrogen carbonate solution and water, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; n - hexane : ethyl acetate = 3 : 1 ), and recrystallized from n-hexane/ethyl acetate to give 2-[(2-benzofuranyl)methylaminocarbonyl]quinoxaline (0.43 g) as colorless flakes.
M.p. 155-156°C Example 4
2-[(4-Morpholinocarbonylmethoxybenzyl)aminocarbonyl]-3 - methylquinoxaline (2.2 g) is dissolved in methylene chloride (30 ml), and thereto is added m-chloroperbenzoic acid (1.3 g) at room temperature, and the mixture is stirred for one day. To the mixture is added chloroform, and the organic layer is washed successively with aqueous sodium thiosulfate solution, saturated aqueous sodium hydrogen carbonate solution, and water, and dried over anhydrous sodium sulfate. The mixture is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; ethyl acetate), and recrystallized from acetonitrile to give 2-[(4 - morpholinocarbonylmethoxybenzyl)aminocarbonyl]-3-methylquinoxalin-4 - oxide (1.5 g) as colorless needles. M.p. 142-143°C
Using the suitable starting compounds, there are obtained the compounds of Examples 28-103, 125, 126, 128, 130-135, 137, 138, 141 , 143 -
146, 148, 150, 152, 154-157, 159, 161 , 163, 165, 167, 169, 171 , 173, 175, 177 ■ 184, 187-189, 191 , 192, 194, 196-201 , 203-205, 207, 209-213, 216, 219, 220, 224, 226, 228-230, 233, 235, 236, 239, 240 and the following Examples 435 - 440, 442-479 and 484-487 in the same manner as in Example 4. Example 5
2-Cinnamylaminocarbonyl-3-methylquinoxaline (1.6 g) is dissolved in dimethylformamide (15 ml), and thereto is added sodium hydride (160 mg) under ice-cooling. The mixture is stirred at the same temperature for 30 minutes, and thereto is added methyl iodide (0.52 g), and the mixture is stirred at room temperature for two hours. The mixture is poured into ice-water, and extracted with diethyl ether. The extract is washed with water, dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; n - hexane : ethyl acetate = 2 : 1 ) to give 2-(N-cinnamyl-N-methylaminocarbonyl)-3 methylquinoxaline (0.8 g) as pale yellow liquid.
1H-NMR (CDCI3) δ ppm: 2.78, 2.79 (3H, s), 2.92, 3.24 (3H, s), 3.98, 4.43 (2H, d, J=6 Hz), 6.10-6.40 (1 H, m), 6.40, 6.70 (1 H, d, J=16 Hz), 7.20-7.50 (5H, m), 7.70-7.85 (2H, m), 8.00-8.15 (2H, m)
Using the suitable starting compounds, there are obtained the compounds of Examples 44, 66, 107, 110, 135, 138, 150, 151 , 152, 153, 175, 176, 178, 186, 187, 191 and 192 in the same manner as in Example 5. Example 6
2-[(5-Aminobenzofuran-2-yl)methylaminocarbonyl]-3 - methylquinoxalin-4-oxide (0.4 g) is suspended in pyridine (6 ml), and thereto is added dropwise with stirring acetic anhydride (0.26 g) under ice-cooling. The mixture is stirred at room temperature for one day, and poured into ice-water. The precipitated crystals are collected by filtration, washed with water, and the resulting crude crystals are recrystallized from acetonitrile to give 2-[(5 - acetylaminobenzofuran-2-yl)methylaminocarbonyl]-3-methylquinoxalin-4-oxide (0.4 g) as pale yellow needles. M.p. 183-184°C Using the suitable starting compounds, there are obtained the compounds of Examples 84 and 85 in the same manner as in Example 6. Example 7
2-[(5-Aminobenzofuran-2-yl)methylaminocarbonyl]-3-methyl - quinoxalin-4-oxide (0.8 g) is dissolved in dimethylformamide (15 ml), and thereto are added potassium carbonate (0.5 g) and N-chloroacetylmorpholine (0.37 g). The mixture is stirred at 70°C for four hours, and evaporated to remove the solvent. To the residue is added water, and the mixture is extracted with chloroform, washed with water, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; ethyl acetate), to convert the resultant to an oxalate thereof, and recrystallized from ethanol to give 2-[(5 - morpholinocarbonylmethylaminobenzofuran-2-yl)methylaminocarbonyl]-3 - methylquinoxalin-4-oxide (40 mg) as pale brown granules. M.p. 159-167°C (decomposed) 1H-NMR (CDCI3) δ ppm: 3.09 (3H, s), 3.40-3.55 (2H, m), 3.55-3.85 (6H, m), 3.90 (2H, s), 4.78 (2H, d, J=6 Hz), 6.60 (1 H, s), 6.65 (1 H, d, J=7 Hz), 6.67 (1 H, s), 7.28 (1 H, d, J=7 Hz), 7.75-7.85 (2H, m), 8.05-8.15 (1 H, m), 8.47 (1 H, brs), 8.50-8.60 (1H, m) Example 8
2-[(5-Ethoxycarbonylbenzofuran-2-yl)methylaminocarbonyl]-3 - methylquinoxalin-4-oxide (4.2 g) is added to a solution of sodium hydroxide (1.4 g) in methanol (50 ml) and water (14 ml), and the mixture is stirred at room temperature overnight. The mixture is evaporated to remove methanol, and to the resultant is added water and acidified with hydrochloric acid, and the precipitated crystals are collected by filtration, washed with water, and dried to give 2-[(5-carboxybenzofuran-2-yl)methylaminocarbonyl]-3-methylquinoxalin-4 oxide (3.8 g) as white powder.
M.p. 251 -252°C (decomposed) Example 9
2-[(6-Methoxymethoxy-3-methylbenzofuran-2-yl)methylamino - carbonyl]-3-methylquinoxalin-4-oxide (2.1 g) is dissolved in tetrahydrofuran (20 ml) and methanol (20 ml), and to the mixture is added 6N hydrochloric acid (10 ml), and the mixture is refluxed for one hour. The mixture is evaporated to remove the solvent, and the residue is extracted with chloroform. The extract is washed with saturated aqueous sodium hydrogen carbonate solution, water and brine, and dried over anhydrous sodium sulfate. The solvent is evaporated to remove the solvent, and the residue is recrystallized from dimethyl - formamide/water to give 2-[(6-hydroxy-3-methylbenzofuran-2-yl)methylamino - carbonyl]-3-methylquinoxalin-4-oxide (1.6 g) give as yellow needles. M.p. 222-223°C (decomposed) Example 10 2-[(4-Hydroxy-3-methylbenzofuran-2-yl)methylaminocarbonyl]-3 - methylquinoxalin-4-oxide (0.55 g) is dissolved in dimethylformamide (4 ml), and to the mixture are added potassium carbonate (0.41 g) and methyl iodide (0.19 ml), and the mixture is stirred at 60°C for four hours. To the mixture is added water, and the precipitated crystals are collected by filtration, and washed with water. The crude crystals are recrystallized from ethyl acetate/n - hexane to give 2-[(4-methoxy-3-methylbenzofuran-2-yl)methylaminocarbonyl] - 3-methylquinoxalin-4-oxide (0.41 g) as yellow prisms. M.p. 196-197°C Example 11
2-[(Benzofuran-2-yl)methylaminocarbonyl]-3-methylquinoxalin-4 - oxide (0.8 g) is dissolved in chloroform (10 ml), and thereto is added N - bromosuccinimide (0.47 g), and the mixture is refluxed for 7 hours. The mixture is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; n-hexane : ethyl acetate = 2 : 1), and recrystallized from ethyl acetate/n-hexane to give 2-[(3-bromobenzofuran-2 - yl)methylaminocarbonyl]-3-methylquinoxalin-4-oxide (0.44 g) as colorless needles. M.p. 170-171 °C
Using the suitable starting compounds, there are obtained the compounds of Examples 31 , 34, 38, 88, 93, 98, 119, 124, 125, 131 and 139 in the same manner as in Example 11.
Example 12 2-[(4-Methoxybenzyl)aminocarbonyl]-3-methylquinoxaline (10.5 g) is dissolved in dry methylene chloride (150 ml), and thereto is added dropwise a 1 M solution of boron tribromide in methylene chloride (105 ml) under ice-cooling. The mixture is stirred at room temperature for two days, cooled, decomposed with methanol, and evaporated to remove the solvent. To the residue is added water, and the mixture is neutralized with sodium hydrogen carbonate, and the precipitated crystals are collected by filtration, washed with water, and dried. The residue is recrystallized from ethanol to give 2-[(4-hydroxybenzyl)aminocarbonyl]-3-methylquinoxaline (10.0 g) as colorless needles. M.p. 211-214°C
Example 13
2-{[5-(1 -Acetoxyethyl)benzofuran-2-yl]methylaminocarbonyl}-3 - methylquinoxalin-4-oxide (4.5 g) is dissolved in methanol (90 ml), and thereto is added potassium carbonate (1.8 g), and the mixture is stirred at room temperature overnight. The mixture is evaporated to remove the solvent, and to the residue is added water. The mixture is extracted with chloroform, washed with water, and dried over anhydrous sodium sulfate. The mixture is evaporated to remove the solvent, and the crude crystals are recrystallized from ethyl acetate/n-hexane to give 2-{[5-(1-hydroxyethyl)benzofuran-2-yl]methyl - aminocarbonyl}-3-methylquinoxalin-4-oxide (3.4 g) as colorless granules. M.p. 112-114°C Example 14 2-{[5-(1 -Hydroxyethyl)benzofuran-2-yl]methylaminocarbonyl}-3 - methylquinoxalin-4-oxide (0.8 g) is dissolved in chloroform (30 ml), and thereto is added manganese dioxide (3.6 g), and the mixture is refluxed for 6 hours. The reaction solution is filtered through celite, and concentrated. The residue is recrystallized from ethyl acetate/n-hexane to give 2-[(5-acetylbenzofuran-2 - yl)methylaminocarbonyl]-3-methylquinoxalin-4-oxide (0.5 g) as pale yellow granules.
M.p. 205-206°C Example 15
2-[(5-Acetylbenzofuran-2-yl)methylaminocarbonyl]-3 - methylquinoxalin-4-oxide (0.7 g) is dissolved in anhydrous tetrahydrofuran (20 ml), and thereto is added dropwise a 1 M solution of methylmagnesium bromide in diethyl ether (2.5 ml) under ice-cooling. The mixture is stirred at room temperature for three hours, and poured into ice-aqueous ammonium chloride solution. The mixture is extracted with chloroform, and the extract is washed with water and brine, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; n-hexane : ethyl acetate = 1 : 1 ), and recrystallized from n-hexane/ethyl acetate to give 2-{[5-(1-hydroxy-1 - methylethyl)benzofuran-2-yl]methylaminocarbonyl}-3-methylquinoxalin-4-oxide (0.1 g) as pale yellow prisms.
M.p. 147-150°C Example 16
2-{[5-(5-Tetrazolyl)benzofuran-2-yl]methylaminocarbonyl}-3 - methylquinoxalin-4-oxide (1.4 g) is dissolved in dimethylformamide (15 ml), and thereto are added potassium carbonate (0.97 g) and methyl iodide (0.44 g), and the mixture is stirred at room temperature for four hours. The reaction solution is poured into ice-water, and the precipitated crystals are collected by filtration, and recrystallized from dimethylformamide/ethanol to give 2-{[5-(2- methyl-5-tetrazolyl)benzofuran-2-yl]methylaminocarbonyl}-3-methylquinoxalin - 4-oxide (0.48 g) as white powder. M.p. 206-209°C
Using the suitable starting compounds, there are obtained the compounds of Examples 36 and 161-164 in the same manner as in Example 16.
Example 17
2-[(4-Methoxycarbonylmethoxybenzyl)aminocarbonyl]-3 - methylquinoxaline (3.65 g) is dissolved in methanol (50 ml), and thereto is added 2N sodium hydroxide (6 ml), and the mixture is stirred at room temperature for two hours. The mixture is evaporated to remove the solvent, and to the resultant is added water. The mixture is acidified with hydrochloric acid, and the precipitated crystals are collected by filtration, washed with water, and dried to give 2-[(4-carboxymethoxybenzyl)aminocarbonyl]-3-methyl - quinoxaline (3.40 g) as white powder.
1H-NMR (DMSO-d6) δ ppm: 2.83 (3H, s), 4.48 (2H, d, J=6 Hz), 4.66 (2H, s), 6.91 (2H, d, J=9 Hz), 7.33 (2H, d, J=9 Hz), 7.8-8.0 (2H, m), 8.0-8.2 (2H, m), 9.33 (1 H, t, J=6 Hz)
Using the suitable starting compounds, there is obtained the compound of Example 49 in the same manner as in Example 17.
Example 18
2-[(4-Carboxymethoxybenzyl)aminocarbonyl]-3 - methylquinoxaline (1.05 g) is dissolved in dimethylformamide (10 ml), and thereto is added furfurylamine (0.35 g), and thereto are added dropwise successively diethyl cyanophosphate (0.6 g) and triethylamine (0.6 g) under ice cooling. The mixture is stirred at room temperature overnight, and poured into ice-water, and the precipitated crystals are collected by filtration. The crystals are recrystallized from acetone/n-hexane to give 2-[(4-furfurylaminocarbonyl - methoxybenzylaminocarbonyl]-3-methylquinoxaline (0.92 g) as white powder. M.p. 175-176°C
Example 19
2-[(4-Methoxycarbonylmethoxybenzyl)aminocarbonyl]-3- methylquinoxaline (0.73 g) and 2-methoxyethylamine (1.1 ml) are dissolved in toluene (10 ml), and the mixture is refluxed for three hours. The mixture is evaporated to remove the solvent, and the residue is recrystallized from ethyl acetate to give 2-{[4-(2-methoxyethylaminocarbonylmethoxy)benzyl]amino - carbonyl}-3-methylquinoxaline (0.95 g) as white powder.
M.p. 138-140°C
Using the suitable starting compounds, there are obtained the compounds of Examples 46, 47, 66, 82, 83, 109, 110, 127, 138, 146-153, 157 - 159, 161-170, 173-175, 186, 187, 191-193, 195 and 196 in the same manner as in Example 18 or 19.
Example 20
2-[(4-Hydroxybenzyl)aminocarbonyl]-3-methylquinoxaline (1.8 g) is dissolved in acetic acid (30 ml) and chloroform (150 ml), and thereto is added dropwise a solution of bromine (0.32 ml) in acetic acid (5 ml) at room temperature, and the mixture is stirred at the same temperature for three hours. The reaction solution is washed with saturated sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent to give 2-[(3-bromo-4-hydroxybenzyl)aminocarbonyl]-3 - methylquinoxaline (1.0 g) as yellow powder. The above product is reacted with N-chloroacetylmorpholine in the same manner as in Example 10, and recrystallized from ethyl acetate/n - hexane to give 2-[(3-bromo-4-morpholinocarbonylmethoxybenzyl)amino - carbonyl]-3-methylquinoxaline (0.6 g) as colorless needles. M.p. 142-143°C Using the suitable starting compounds, there are obtained the compounds of Examples 45, 51 , 56, 58-60, 64-66, 78, 79, 82-83, 87, 106, 108, 110, 116, 117, 120, 121 , 123, 126, 127, 138, 140-142, 144, 146-153, 156-164, 167-177, 182, 185-193, 195, 196, 202, 207, 210-212, 222-224, 230-234 and 241 in the same manner as in Example 10 or 20. Example 21
2-[(4-Methoxycarbonylbenzyl)aminocarbony]-3-methyl - quinoxaline (0.75 g) is dissolved in tetrahydrofuran (40 ml), and thereto is added dropwise with stirring lithium aluminum hydride (0.17 g) under ice- cooling. The mixture is stirred at the same temperature for three hours, and thereto are added successively aqueous 10 % sodium hydroxide solution (0.3 ml) and water (0.3 ml), and decomposed. The mixture is filtered through celite, and the filtrate is dried over anhydrous sodium sulfate, and evaporated to remove the solvent to give 2-[(4-hydroxymethylbenzyl)aminocarbonyl]-3 - methylquinoxaline (0.44 g) as yellow powder.
1H-NMR (CDCI3) δ ppm: 1.75 (1H, t, J=6 Hz), 4.70 (4H, d, J=6 Hz), 7.3 - 7.5 (4H, m), 7.7-7.9 (2H, m), 8.0-8.1 (2H, m), 8.39 (1 H, brs) Example 22 Lithium aluminum hydride (1.9 g) is suspended in tetrahydrofuran
(100 ml), and thereto is added dropwise and gradually a solution of 2-[(4 - methoxycarbonylmethoxybenzyl)aminocarbonyl]-3-methylquinoxaline (9.5 g) in tetrahydrofuran (50 ml) under ice-cooling. After addition, the mixture is stirred at the same temperature for 30 minutes, and further stirred at room temperature for two hours. After the reaction is complete, to the reaction mixture is added ethyl acetate under ice-cooling, and further added saturated aqueous ammonium chloride solution. The insoluble materials are removed by filtration, and extracted with ethyl acetate. The extract is dried over anhydrous sodium sulfate and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; ethyl acetate : n-hexane = 1 : 4) to give 2 -
{[4-(2-hydroxyethoxy)benzyl]aminocarbonyl}-3-methylquinoxaline (1.0 g) as yellow liquid.
1H-NMR (CDCI3) δ ppm: 2.25 (1 H, br), 3.17 (3H, s), 3.9-4.1 (4H, m), 4.63 (2H, d, J=6 Hz), 6.92 (2H, d, J=7 Hz), 7.34 (2H, d, J=7 Hz), 7.7-7.9 (2H, m), 8.0 - 8.1 (2H, m), 8.34 (1 H, br)
Example 23
2-{[4-(2-Hydroxyethoxy)benzyl]aminocarbony}-3-methyl - quinoxaline (0.2 g) and triphenylphosphine (0.17 g) is dissolved in carbon tetrachloride (10 ml), and the mixture is refluxed for 1.5 hour. After the reaction is complete, the mixture is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; ethyl acetate : n-hexane = 1 : 2) to give 2-{[4-(2-chloroethoxy)benzyl]aminocarbonyl}-3-methyl- quinoxaline (0.10 g) as yellow liquid.
1H-NMR (CDCI3) δ ppm: 3.17 (3H, s), 3.82 (2H, t, J=6 Hz), 4.24 (2H, t,
J=6 Hz), 4.64 (2H, d, J=6 Hz), 6.93 (2H, d, J=9 Hz), 7.35 (2H, d, J=9 Hz), 7.7-7.9 (2H, m), 8.0-8.1 (2H, m), 8.33 (1H, br) Example 24
2-{[(4-Chloroethoxy)benzyl]aminocarbony}-3-methylquinoxaline (100 mg) and morpholine (0.21 ml) are dissolved in dimethylformamide (10 ml), and thereto are added sodium iodide (1.2 g) and potassium carbonate (300 mg), and the mixture is heated at 60°C for 7.5 hours. After the reaction is complete, the mixture is poured into ice-water, and extracted with ethyl acetate. The organic layer is washed with water and brine, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; ethyl acetate : n-hexane = 2 : 3) to give yellow liquid, which is dissolved in ethanol, and thereto is added ethanol-hydrochloric acid solution, and concentrated to dryness. The precipitated crystals are recrystallized from ethanol/diethyl ether to give 2-{[4-(2-morpholinoethoxy)benzyl]aminocarbonyl}-3-methylquinoxaline hydrochloride (70 mg) as yellow powder. M.p. 155-158°C (decomposed) Using the suitable starting compounds, there is obtained the compound of Example 203 in the same manner as in Example 24. Example 25
2-{[4-(2-Methyl-1 ,3-dioxolan-2-yl)benzyl]aminocarbonyl}-3 - methylquinoxalin-4-oxide (1.3 g) is dissolved in acetone (20 ml) and dichloro - methane (10 ml), and thereto is added p-toluenesulfonic acid (60 mg), and the mixture is stirred at room temperature for five hours. The mixture is evaporated to remove the solvent, and the residue is extracted with ethyl acetate. The extract is washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is recrystallized from ethanol to give 2-[(4 - acetylbenzyl)aminocarbonyl]-3-methylquinoxalin-4-oxide (1.0 g) as pale yellow needles. M.p. 165-167°C Example 26
2-[2-(4-Methoxyρhenylthio)ethylaminocarbonyl]-3 - methylquinoxalin-4-oxide (2.4 g) is dissolved in methylene chloride (40 ml), and thereto are gradually added m-chloroperbenzoic acid (1.4 g) under ice - cooling, and the mixture is stirred at the same temperature for one hour. The reaction solution is washed with aqueous sodium thiosulfate solution, saturated sodium hydrogen carbonate solution and water, and dried over anhydrous sodium sulfate. The mixture is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; ethyl acetate), and recrystallized from ethanol to give 2-[2-(4-methoxyphenylsuifinyl)ethyl - aminocarbonyl]-3-methylquinoxalin-4-oxide (1.8 g) as colorless needles. M.p. 156-157°C
Using the suitable starting compounds, there are obtained the compounds of Examples 212 and 217-220 in the same manner as in Example 26.
Example 27
2-[2-(4-Methoxyphenylthio)ethylaminocarbonyl]-3-methyl - quinoxalin-4-oxide (2.4 g) is dissolved in methylene chloride (40 ml), and thereto is added gradually m-chloroperbenzoic acid (2.8 g) under ice-cooling. The mixture is reacted at the same temperature for one hour, and the reaction solution is washed with aqueous sodium thiosulfate solution, saturated sodium hydrogen carbonate solution and water, and dried over anhydrous sodium sulfate. The mixture is evaporated to remove the solvent, and the residue is recrystallized from ethanol to give 2-[2-(4-methoxyphenylsulfonyl)ethyl - aminocarbonyl]-3-methylquinoxalin-4-oxide (2.1 g) as colorless needles. M.p. 148-150°C
Using the suitable starting compounds, there are obtained the compounds of Examples 218 and 220 in the same manner as in Example 27. Using the suitable starting compounds, there are obtained the compounds as listed in Table 5 in the same manner as in Example 1 , 2 or 3. Table 5
Figure imgf000307_0001
Example 28 Structure:
Figure imgf000307_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 154-157 Form: Free
Example 29 Structure:
Figure imgf000307_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 169-170 Form: Free Example 30 Structure:
Figure imgf000308_0001
R1: H R2 : CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 143-144 Form: Free
Example 31 Structure:
Figure imgf000308_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles Solvent for recrystal.: Ethanol M.p. (°C): 121-128 Form: Free
Example 32 Structure:
Figure imgf000308_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Orange granules Solvent for recrystal.: Ethanol M.p. (°C): 173-174 Form: Free Example 33 Structure:
Figure imgf000309_0001
R1: H R : CH3 m: 1 n: 0
Crystalline form: Pale yellow granules Solvent for recrystal.: Dimethylformamide/water M.p. (°C): 192-195 Form: Free
Example 34 Structure:
Figure imgf000309_0002
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethanol/water
M.p. (°C): 180-182
Form: Free
Example 35 Structure:
Figure imgf000309_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless granules Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 149-151 Form: Free Example 36 Structure:
Figure imgf000310_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 171-177
Form: Free
Example 37 Structure:
Figure imgf000310_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow prisms Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 210-212 (decomposed) Form: Free
Example 38 Structure:
Figure imgf000310_0003
R1: H R2; CH3 m: 1 n: 0
Crystalline form: Colorless flakes Solvent for recrystal.: Acetonitrile M.p. (°C): 215-217 (decomposed) Form: Free Example 39 Structure:
Figure imgf000311_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 183-184
Form: Free
Example 40 Structure:
Figure imgf000311_0002
R1: H R : CH3 m: 1 n: 0
Crystalline form: Yellow powder
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 182-183
Form: Free
Example 41 Structure:
Figure imgf000311_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale red needles Solvent for recrystal.: Ethanol M.p. (°C): 173-174 Form: Free Example 42 Structure:
Figure imgf000312_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow granules Solvent for recrystal.: Acetonitrile M.p. (°C): 214-215 (decomposed) Form: Free
Example 43 Structure:
Figure imgf000312_0002
Crystalline form: Pale yellow needles Solvent for recrystal.: Ethanol M.p. (°C): 187-189 Form: Free
Figure imgf000312_0003
Example 45 Structure:
Figure imgf000313_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 159-160 Form: Free
Example 46 Structure:
Figure imgf000313_0002
R1: H R2; CH3 m: 1 n: 0
Crystalline form: White powder Solvent for recrystal.: 2-Propanol M.p. (°C): 183-184 Form: Free
Example 47 Structure:
Figure imgf000313_0003
R1: H R : CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: 2-Propanol M.p. (°C): 146-148 Form: Free Example 48 Structure:
Figure imgf000314_0001
Crystalline form: Pale yellow prisms Solvent for recrystal.: Acetonitrile M.p. (°C): 168-169 Form: Free
Example 49 Structure:
Figure imgf000314_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol/water
M.p. (°C): 202-204
Form: Free
Example 50 Structure:
Figure imgf000314_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder M.p. (°C): 251-252 (decomposed) Form: Free Example 51 Structure:
Figure imgf000315_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 120-122
Form: Free
Example 52 Structure:
Figure imgf000315_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale brown granules Solvent for recrystal.: Ethanol M.p. (°C): 159-167 (decomposed) Form: Oxalate
Example 53 Structure:
Figure imgf000315_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 222-223 (decomposed)
Form: Free Example 54 Structure:
Figure imgf000316_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 156-158
Form: Free
Example 55 Structure:
Figure imgf000316_0002
R1: H R : CH3 m: 1 n: 0
Crystalline form: Yellow granules
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 237-238 (decomposed)
Form: Free
Example 56 Structure:
Figure imgf000316_0003
R1: H R2; CH3 m: 1 n: 0
Crystalline form: White powder M.p. (°C): 130-132 Form: Free Example 57 Structure:
Figure imgf000317_0001
R : H R2: CH3 m: 1 n: 0
Crystalline form: Yellow prisms
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 196-197
Form: Free
Example 58 Structure:
Figure imgf000317_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow plates Solvent for recrystal.: Ethanol M.p. (°C): 123-124 Form: Free
Example 59 Structure:
Figure imgf000317_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 177-178
Form: Free Example 60 Structure:
Figure imgf000318_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Dimethylformamide
M.p. (°C): 155-156
Form: Free
Example 61 Structure:
Figure imgf000318_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 220-221
Form: Free
Example 62 Structure:
Figure imgf000318_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 170-171
Form: Free Example 63 Structure:
Figure imgf000319_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 125-126
Form: Free
Example 64 Structure:
Figure imgf000319_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder M.p. (°C): 166-168 Form: Free
Example 65 Structure:
Figure imgf000319_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder M.p. (°C): 114-116 Form: Free Example 66 Structure:
Figure imgf000320_0001
R1: H R2: CH3 m: 1 n:0
Crystalline form: White powder Solvent for recrystal.: Acetonitrile M.p. (°C): 184-186 Form: Free
Example 67 Structure:
Figure imgf000320_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 160-161
Form: Free
Example 68 Structure:
Figure imgf000320_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 70-72
Form: Free Example 69 Structure:
Figure imgf000321_0001
R : H R2: CH3 m: 1 n: 0
Crystalline form: Colorless granules Solvent for recrystal.: Ethanol M.p. (°C): 89-90 Form: Free
Example 70 Structure:
Figure imgf000321_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless granules Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 112-114 Form: Free
Example 71 Structure:
Figure imgf000321_0003
Crystalline form: Pale yellow rods Solvent for recrystal.: Acetonitrile M.p. (°C): 184-185 Form: Free Example 72 Structure:
Figure imgf000322_0001
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 153-155 Form: Free
Example 73 Structure:
Figure imgf000322_0002
R : H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 160-162 Form: Free
Example 74 Structure:
Figure imgf000322_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 143-144
Form: Free Example 75 Structure:
Figure imgf000323_0001
R : H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 199-201
Form: Free
Example 76 Structure:
Figure imgf000323_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow powder
Solvent for recrystal.: Dimethylformamide/ethanol
M.p. (°C): 256-258 (decomposed)
Form: Free
Example 77 Structure:
Figure imgf000323_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow granules
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 205-206
Form: Free Example 78 Structure:
Figure imgf000324_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethanol
M.p. (°C): 154-155
Form: Free
Example 79 Structure:
Figure imgf000324_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless prisms Solvent for recrystal.: Ethanol M.p. (°C): 169-170 Form: Free
Example 80 Structure:
Figure imgf000324_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Brown powder Solvent for recrystal.: Ethanol M.p. (°C): 133-135 Form: Free Example 81 Structure:
Figure imgf000325_0001
R : H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow plates Solvent for recrystal.: Ethanol M.p. (°C): 112-114 Form: Free
Example 82 Structure:
Figure imgf000325_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow rods
Solvent for recrystal.: Dimethylformamide/ethanol
M.p. (°C): 189-190
Form: Free
Example 83 Structure:
Figure imgf000325_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow powder
Solvent for recrystal.: Dimethylformamide/ethanol
M.p. (°C): 177-178
Form: Free Example 84 Structure:
Figure imgf000326_0001
R1; H R2: CH3 m: 1 n: 0
Crystalline form: White powder
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 230-232
Form: Free
Example 85 Structure:
Figure imgf000326_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 218-220 Form: Free
Example 86 Structure:
Figure imgf000326_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 214-215
Form: Free Example 87 Structure:
Figure imgf000327_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder M.p. (°C): 146-147 Form: Free
Example 88 Structure:
Figure imgf000327_0002
R1; H R2: CH3 m: 1 n: 0
Crystalline form: Colorless flakes
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 180-181
Form: Free
Example 89 Structure:
Figure imgf000327_0003
Crystalline form: Colorless needles Solvent for recrystal.: Chloroform/n-hexane M.p. (°C): 186-188 Form: Free Example 90 Structure:
Figure imgf000328_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow powder
Solvent for recrystal.: Diethyl ether/n-hexane
M.p. (°C): 80-83
Form: Free
Example 91 Structure:
Figure imgf000328_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Brown prisms Solvent for recrystal.: Acetone/n-hexane M.p. (°C): 179-180 Form: Free
Example 92 Structure
Figure imgf000328_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethanol M.p. (°C): 206-207 Form: Free Example 93 Structure:
Figure imgf000329_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 139-141 Form: Free
Example 94 Structure:
Figure imgf000329_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow prisms Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 147-150 Form: Free
Example 95 Structure:
Figure imgf000329_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethanol M.p. (°C): 133-134 Form: Free Example 96 Structure:
Figure imgf000330_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder
Solvent for recrystal.: Dimethylformamide/ethanol
M.p. (°C): 206-209
Form: Free
Example 97 Structure:
Figure imgf000330_0002
R -: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 117-119
Form: Free
Example 98 Structure:
Figure imgf000330_0003
R1; H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow powder Solvent for recrystal.: Ethanol M.p. (°C): 200-202 (decomposed) Form: Free Example 99 Structure:
Figure imgf000331_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale brown needles
Solvent for recrystal.: Acetone/n-hexane
M.p. (°C): 199-200
Form: Free
Example 100 Structure:
Figure imgf000331_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 167-168 Form: Free
Example 101 Structure:
Figure imgf000331_0003
R1: H R2: CH3 m: 0 n: 1
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 152-153
Form: Free Example 102 Structure:
Figure imgf000332_0001
R : H R2: CH3 m: 1 n: 1
Crystalline form: Yellow powder Solvent for recrystal.: Ethanol M.p. (°C): 130-133 (decomposed) Form: Free
Example 103 Structure:
Figure imgf000332_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 143-144 Form: Free
Example 104 Structure:
Figure imgf000332_0003
R : H R2: CH3 m: 0 n: 0
Crystalline form: Pale brown needles
Solvent for recrystal.: Diisopropyl ether/n-hexane
Form: Free Example 105 Structure:
Figure imgf000333_0001
R : H R2: CH3 m: 0 n: 0
Crystalline form: Pale brown prisms
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 122-124
Form: Free
Example 106 Structure:
Figure imgf000333_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow needles Form: Free
Example 107 Structure:
Figure imgf000333_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow needles Form: Free Example 108 Structure:
Figure imgf000334_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 99-100 Form: Free
Example 109 Structure:
Figure imgf000334_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 124-125 Form: Free
Example 110 Structure:
O
Figure imgf000334_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless flakes Solvent for recrystal.: Ethanol/water M.p. (°C): 139-140 Form: Free Example 111 Structure:
Figure imgf000335_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale brown oil Form: Free
Example 112 Structure:
Figure imgf000335_0002
R1_ H R2: CH, m: 0 n: 0
Crystalline form: Red powder
Solvent for recrystal.: Diisopropyl ether/n-hexane
M.p. (°C): 148-150
Form: Free
Example 113 Structure:
Figure imgf000335_0003
R : H R2: CH3 m: 0 n: 0
Crystalline form: Yellow prisms Solvent for recrystal.: n-Hexane M.p. (°C): 105-106 Form: Free Example 114 Structure:
- ?C.-N - - ?C.-NHCH2 X^ |v)
XR4
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 135-136 Form: Free
Example 115 Structure:
Figure imgf000336_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow powder
Solvent for recrystal.: Diisopropyl ether/n-hexane
M.p. (°C): 121-122
Form: Free
Example 116 Structure:
Figure imgf000336_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Diisopropyl ether M.p. (°C): 88-89 Form: Free Example 117
Structure:
Figure imgf000337_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow needles Solvent for recrystal.: Diethyl ether M.p. (°C): 129-130 Form: Free
Example 118 Structure:
Figure imgf000337_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane/diethyl ether M.p. (°C): 106-107 Form: Free
Example 1 19 Structure:
Figure imgf000337_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow granules
Solvent for recrystal.: Diisopropyl ether/n-hexane
M.p. (°C): 118-119
Form: Free Example 120 Structure:
Figure imgf000338_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Diisopropyl ether/n-hexane
M.p. (°C): 101-102
Form: Free
Example 121 Structure:
Figure imgf000338_0002
R1 : H R2: CH3 m: 0 n: 0
Crystalline form: Yellow granules Solvent for recrystal.: Diisopropyl ether/n-hexane M.p. (°C): 118-119 Form: Free
Example 122 Structure:
Figure imgf000338_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Orange powder Solvent for recrystal.: Diisopropyl ether/n-hexane M.p. (°C): 184-185 Form: Free Example 123 Structure:
Figure imgf000339_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow plates Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 148-150 Form: Free
Example 124 Structure:
Figure imgf000339_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Diisopropyl ether M.p. (°C): 124-125 Form: Free
Example 125 Structure:
Figure imgf000339_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless flakes
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 122-123
Form: Free Example 126 Structure:
Figure imgf000340_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 115-116 Form: Free
Example 127 Structure:
Figure imgf000340_0002
R1: H R2; CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 142-143 Form: Free
Example 128 Structure: o R3 o „ ιι / ιι /=\
-C-N : -C-NH(CH2)3 -(^ )
R4
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 99-100
Form: Free Example 129 Structure:
Figure imgf000341_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow granules
Solvent for recrystal.: Methanol/water
M.p. (°C): 102-103
Form: Free
Example 130 Structure:
Figure imgf000341_0002
R1 : H R2: CH3 m: 1 n: 0
Crystalline form: Yellow needles Solvent for recrystal.: Ethanol M.p. (°C): 21 1 -213 Form: Free
Example 131 Structure:
Figure imgf000341_0003
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 123-124 Form: Free Example 132 Structure:
Figure imgf000342_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 146-147 Form: Free
Example 133 Structure:
Figure imgf000342_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Orange needles Solvent for recrystal.: Ethanol M.p. (°C): 246-248 (decomposed) Form: Free
Example 134 Structure:
Figure imgf000342_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Orange powder Solvent for recrystal.: Ethanol M.p. (°C): 188-190 Form: Free Example 135 Structure:
Figure imgf000343_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Orange powder Solvent for recrystal.: Acetone Form: Oxalate
Example 136 Structure:
Figure imgf000343_0002
R : H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 211-214 Form: Free
Example 137 Structure:
Figure imgf000343_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow granules Solvent for recrystal.: Ethyl acetate M.p. (°C): 187-192 Form: Free Example 138 Structure:
Figure imgf000344_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate M.p. (°C): 190-199 Form: Free
Example 139 Structure:
Figure imgf000344_0002
R- H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Diisopropyl ether M.p. (°C): 147-148 Form: Free
Example 140 Structure:
Figure imgf000344_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow powder
Solvent for recrystal.: Diisopropyl ether
M.p. (°C): 116-117
Form: Free Example 141 Structure:
Figure imgf000345_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Orange powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 120-122
Form: Free
Example 142 Structure:
Figure imgf000345_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 127-128
Form: Free
Example 143 Structure:
Figure imgf000345_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 128-130
Form: Free Example 144 Structure:
Figure imgf000346_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 123-124
Form: Free
Example 145 Structure:
Figure imgf000346_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow prisms
Solvent for recrystal.: Isopropanol/diisopropyl ether
M.p. (°C): 171 -173
Form: Free
Example 146 Structure:
Figure imgf000346_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow granules
Solvent for recrystal.: Isopropanol/diisopropyl ether
M.p. (°C): 176-177
Form: Free Example 147 Structure:
Figure imgf000347_0001
R : H R2: CH3 m: 0 n: 0
Crystalline form: Colorless flakes
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 148-149
Form: Free
Example 148 Structure:
Figure imgf000347_0002
R1: H R2: CH3 m: 1 n: 0 Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n- hexane M.p. (°C): 119-120 Form: Free
Example 149 Structure:
Figure imgf000347_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: White powder M.p. (°C): 135-137 Form: Free Example 150 Structure:
Figure imgf000348_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 118-119
Form: Free
Example 151 Structure:
Figure imgf000348_0002
Crystalline form: Colorless prisms Solvent for recrystal.: Acetone M.p. (°C): 135-137 Form: Free
Example 152 Structure:
Figure imgf000348_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Acetone/n-hexane M.p. (°C): 196-198 Form: Free Example 153 Structure:
Figure imgf000349_0001
R : H R2: CH3 m: 0 n: 0
Crystalline form: Colorless flakes
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 133-134
Form: Free
Example 154 Structure:
Figure imgf000349_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Dimethylformamide M.p. (°C): 225-226 Form: Free
Example 155 Structure:
Figure imgf000349_0003
R1; H R2: CH, m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 98-100
Form: Free Example 156 Structure:
Figure imgf000350_0001
R : H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 100-101 Form: Free
Example 157 Structure:
Figure imgf000350_0002
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 144-145 Form: Free
Example 158 Structure:
Figure imgf000350_0003
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 133-134 Form: Free Example 159 Structure:
Figure imgf000351_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow powder
M.p. (°C): 83-87
Form: Free
Example 160 Structure:
Figure imgf000351_0002
R : H R2: CH3 m: 0 n: 0
Crystalline form: White powder Solvent for recrystal.: Acetone/n-hexane M.p. (°C): 175-176 Form: Free
Example 161 Structure:
Figure imgf000351_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder
Solvent for recrystal.: Ethanol/diethyl ether
M.p. (°C): 246-247 (decomposed)
Form: Hydrochloride Example 162 Structure:
Figure imgf000352_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless flakes
Solvent for recrystal.: Methanol/diethyl ether
M.p. (°C): 214-215
Form: Hydrochloride
Example 163 Structure:
Figure imgf000352_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder M.p. (°C): 212-215 (decomposed) Form: Hydrochloride
Example 164 Structure:
Figure imgf000352_0003
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 139-141 Form: Free Example 165 Structure:
N
Figure imgf000353_0001
R : H R2: CH3 m: 1 n: 0
Crystalline form: Colorless granules Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 170-171 Form: Free
Example 166 Structure:
Figure imgf000353_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless granules Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 152-153 Form: Free
Example 167 Structure:
Figure imgf000353_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 165-166 Form: Free Example 168 Structure:
Figure imgf000354_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 142-143 Form: Free
Example 169 Structure:
Figure imgf000354_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder M.p. (°C): 134-135 Form: Free
Example 170 Structure:
Figure imgf000354_0003
R : H R2: CH3 m: 0 n: 0
Crystalline form: Colorless flakes
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 126-128
Form: Free Example 171 Structure:
Figure imgf000355_0001
R1: H R2: CH 1?3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 126-128
Form: Free
Example 172 Structure:
Figure imgf000355_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: White powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 106-107
Form: Free
Example 173 Structure:
Figure imgf000355_0003
R\ H R2: CH3 m: 1 n: 0
Crystalline form: Colorless prisms Solvent for recrystal.: Acetone/n-hexane M.p. (°C): 167-169 Form: Free Example 174 Structure:
Figure imgf000356_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 129-130 Form: Free
Example 175 Structure:
Figure imgf000356_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 135-136
Form: Free
Example 176 Structure:
Figure imgf000356_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 138-140 Form: Free Example 177 Structure:
Figure imgf000357_0001
R1; H R2: Cl m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate M.p. (°C): 140-141 Form: Free
Example 178 Structure:
Figure imgf000357_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 146-147
Form: Free
Example 179 Structure:
Figure imgf000357_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 154-155 Form: Free Example 180 Structure:
Figure imgf000358_0001
R1; H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 155-156 Form: Free
Example 181 Structure:
Figure imgf000358_0002
R : H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane/diethyl ether M.p. (°C): 67-69 Form: Free
Example 182 Structure:
Figure imgf000358_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Brown powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 132-133 Form: Free Example 183 Structure:
Figure imgf000359_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 174-175 Form: Free
Example 184 Structure:
: _c-NHCH2— f> χ) °2"*
Figure imgf000359_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 156-158 Form: Free
Example 185 Structure:
Figure imgf000359_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 102-103 Form: Free Example 186 Structure:
Figure imgf000360_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow oil Form: Free
Example 187 Structure:
Figure imgf000360_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Yellow oil Form: Free
Example 188 Structure:
Figure imgf000360_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 123-124 Form: Free Example 189 Structure:
Figure imgf000361_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 149-151
Form: Free
Example 190 Structure:
Figure imgf000361_0002
R1 : H R2: CH3 m: 0 n: 0
Crystalline form: : Yellow powder Form: Free
Example 191 Structure:
Figure imgf000361_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless prisms
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 122-123
Form: Free Example 192 Structure:
Figure imgf000362_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder
Solvent for recrystal.: Methanol/diethyl ether
M.p. (°C): 110-112
Form: Free
Example 193 Structure:
Figure imgf000362_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 193-195
Form: Free
Example 194 Structure:
Figure imgf000362_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Diisopropyl ether M.p. (°C): 152-153 Form: Free Example 195 Structure:
Figure imgf000363_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 164-165 Form: Free
Example 196 Structure:
Figure imgf000363_0002
R : H R2: CH3 m: 1 n: 0
Crystalline form: Yellow granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 144-145
Form: Free
Example 197 Structure:
Figure imgf000363_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 195-196 Form: Free Example 198 Structure:
Figure imgf000364_0001
Crystalline form: Pale yellow needles Solvent for recrystal.: Dichloromethane/n-hexane M.p. (°C): 105-107 Form: Free
Example 199 Structure:
Figure imgf000364_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow flakes Solvent for recrystal.: Ethanol M.p. (°C): 159-160 Form: Free
Example 200 Structure:
Figure imgf000364_0003
R : H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles Solvent for recrystal.: Ethanol M.p. (°C): 165-167 Form: Free Example 201 Structure:
C2H5
Figure imgf000365_0001
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 195-196 Form: Free
Example 202 Structure:
Figure imgf000365_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow powder
Solvent for recrystal.: Ethanol/diethyl ether
M.p. (°C): 155-158 (decomposed)
Form: Hydrochloride
Example 203 Structure:
Figure imgf000365_0003
Crystalline form: Yellow granules Solvent for recrystal.: Ethanol/diethyl ether M.p. (°C): 116-118 Form: Hydrochloride Example 204 Structure:
Figure imgf000366_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 118-120 Form: Free
Example 205 Structure:
Figure imgf000366_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 56-58 Form: Free
Example 206 Structure:
Figure imgf000366_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Pale brown prisms Solvent for recrystal.: Isopropanol/water M.p. (°C): 133-134 Form: Free Example 207 Structure:
Figure imgf000367_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 170-171 Form: Free
Example 208 Structure:
Figure imgf000367_0002
R : H R2: CH3 m: 0 n: 0
Crystalline form: Pale yellow oil Form: Free
Example 209 Structure:
Figure imgf000367_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless oil Form: Free Example 210 Structure:
Figure imgf000368_0001
R : H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 76-77 Form: Free
Example 211 Structure:
Figure imgf000368_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 156-157 Form: Free
Example 212 Structure:
Figure imgf000368_0003
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 148-150 Form: Free Example 213 Structure:
Figure imgf000369_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow prisms Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 113-114 Form: Free
Example 214 Structure:
Figure imgf000369_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol/water M.p. (°C): 115-116 Form: Free
Example 215 Structure:
Figure imgf000369_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol/water M.p. (°C): 87-88 Form: Free Example 216 Structure:
Figure imgf000370_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 107-109 Form: Free
Example 217 Structure:
Figure imgf000370_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol/water M.p. (°C): 132-133 Form: Free
Example 218 Structure:
Figure imgf000370_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 162-163 Form: Free Example 219 Structure:
Figure imgf000371_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 156-157 Form: Free
Example 220 Structure:
Figure imgf000371_0002
R : H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 181-182 Form: Free
Example 221 Structure:
Figure imgf000371_0003
R1: H R2: CF3 m: 0 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 155-157
Form: Free Example 222 Structure:
Figure imgf000372_0001
R : H R2: CF3 m: 0 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 115-116
Form: Free
Example 223 Structure:
Figure imgf000372_0002
0 n: 0
Crystalline form: Colorless granules Solvent for recrystal.: n-Hexane/ethyl acetate M.p. (°C): 150-151 Form: Free
Example 224 Structure:
Figure imgf000372_0003
R1: H R2: H m: 1 n: 0
Crystalline form: Pale yellow flakes Solvent for recrystal.: Ethanol M.p. (°C): 126 Form: Free Example 225 Structure:
Figure imgf000373_0001
R1: H R2: H m: 0 n: 0
Crystalline form: Colorless flakes
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 155-156
Form: Free
Example 226 Structure:
Figure imgf000373_0002
R1: H R2: H m: 1 n: 0
Crystalline form: Pale brown flakes Solvent for recrystal.: Acetonitrile M.p. (°C): 211 -213 Form: Free
Example 227 Structure:
Figure imgf000373_0003
R1: H R2: m: 0 n: 0 -O
Crystalline form: Brown granules
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 169-171
Form: Free Example 228 Structure:
Figure imgf000374_0001
R -: H R2: -CH(CH3)2 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 114-116
Form: Free
Example 229 Structure:
Figure imgf000374_0002
orm: ree
Example 230 Structure:
Figure imgf000374_0003
R : H R2: -C2H5 m: 1 n: 0
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 87-89
Form: Free Example 231
Structure:
Figure imgf000375_0001
R1: H R2: -CH(CH3)2 m: 0 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: n-Hexane M.p. (°C): 67-68 Form: Free
Example 232 Structure:
Figure imgf000375_0002
R1: H R2: -C2H5 m: 0 n: 0
Crystalline form: Pale yellow prisms Solvent for recrystal.: n-Hexane M.p. (°C): 82-83 Form: Free
Example 233 Structure:
Figure imgf000375_0003
R1; H R2: m: 1 n: 0 -o
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 157-158
Form: Free Example 234 Structure:
Figure imgf000376_0001
R : H R2: H m: 0 n: 0
Crystalline form: Yellow needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 92-93
Form: Free
Example 235 Structure:
Figure imgf000376_0002
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 173-174
Form: Free
Example 236 Structure:
Form: Free Example 237 Structure:
Figure imgf000377_0001
R1: H R2: -CH2-N O m: 0 n: 0
Crystalline form: White powder Solvent for recrystal.: Ethanol/diethyl ether M.p. (°C): 156-158 (decomposed) Form: Oxalate
Example 238 Structure:
Figure imgf000377_0002
Rl: H R2: -CH2 -N^N m: 0 n: 0
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 118-119
Form: Free
Example 239 Structure: fi /R3 fi
-C-N : — C-NHCH2CH=CH2
Y4
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 116-118 Form: Free Example 240 Structure:
-NHCH2CH=C(CH3)2
Figure imgf000378_0001
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 112-113
Form: Free
Example 241 Structure:
Figure imgf000378_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: White powder Form: Free
Example 242
Structure:
Figure imgf000378_0003
Crystalline form: Yellow powder Form: Free Example 243 Structure:
Figure imgf000379_0001
R1: H R2: CH3 m: 0 n: 0
Crystalline form: White powder Form: Free
Example 244 Structure:
Figure imgf000379_0002
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow powder Form: Free
Example 245 Structure:
Figure imgf000379_0003
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow oil Form: Free
Example 246 Structure:
Figure imgf000379_0004
R1: H R2: CH3 m: 0 n: 0
Crystalline form: Yellow oil Form: Free NMR analysis:
Ex. No. 1H-NMR δ ppm:
(CDCI3); 1.11 (3H, t, J=7 Hz), 1.20 (3H, t, J=7 Hz), 3.17 (3H, s), 3.3 -
186 3.5 (4H, m), 4.6-4.7 (4H, m), 6.89 (1H, d, J=8 Hz), 7.00 (2H, m), 7.30 (1 H, d, J=8 Hz), 7.7-7.9 (2H, m), 8.0-8.1 (2H, m), 8.40 (1 H, brs)
(CDCI3); 1.12 (3H, t, J=7 Hz), 1.21 (3H, t, J=7 Hz), 3.10 (3H, s), 3.3 -
187 3.5 (4H, m), 4.66 (2H, d, J=7 Hz), 4.68 (2H, s), 6.88 (1H, d, J=8 Hz), 7.0-7.1 (2H, m), 7.29 (1 H, d, J=8 Hz), 7.7-7.9 (2H, m), 8.0-8.1 (1 H, m), 8.39 (1 H, br), 8.5-8.6 (1 H, m)
(CDCI3); 3.17 (3H, s), 3.61 (3H, s), 4.63 (2H, d, J=6 Hz), 4.99 (2H, s),
190 6.9-7.0 (4H, m), 7.3-7.4 (4H, m), 7.7-7.9 (2H, m), 8.0-8.1 (2H, m), 8.31 (1 H, brs)
(CDCI3); 2.78, 2.79 (3H, s), 2.92, 3.24 (3H, s), 3.98, 4.43 (2H, d, J=6
208 Hz), 6.10-6.40 (1 H, m), 6.40, 6.70 (1 H, d, J=16 Hz), 7.20-7.50 (5H, m), 7.70-7.85 (2H, m), 8.00-8.15 (2H, m),
(CDCI3); 8.56 (1 H, m), 8.20 (1 H, bit, J=6 Hz), 8.06 (1 H, m), 7.77
209 (2H, m), 7.21 (4H, m), 6.51 (1 H, s), 4.22 (2H, d, J=6 Hz), 3.07 (3H, s), 2.90 (1 H, sept, J=7 Hz), 1.98 (3H, s), 1.25 (6H, d, J=7 Hz)
(CDCI3); 2.25 (1 H, br), 3.17 (3H, s), 3.9-4.1 (4H, m), 4.63 (2H, d, J=6
245 Hz), 6.92 (2H, d, J=7 Hz), 7.34 (2H, d, J=7 Hz), 7.7-7.9 (2H, m), 8.0 - 8.1 (2H, m), 8.34 (1 H, br)
(CDCI3); 3.09 (3H, s), 3.40-3.55 (2H, m), 3.55-3.85 (6H, m), 3.90
52 (2H, s), 4.78 (2H, d, J=6 Hz), 6.60 (1 H, s), 6.65 (1 H, d, J=7 Hz), 6.67 (1 H, s), 7.28 (1 H, d, J=7 Hz), 7.75-7.85 (2H, m), 8.05-8.15 (1 H, m), 8.47 (1 H, brs), 8.50-8.60 (1 H, m)
(CDCI3); 8.05 (3H, m), 7.78 (2H, m), 7.25 (5H, m), 3.56 (2H, q, J=7
104 Hz), 3.14 (3H, s), 2.77 (2H, t, J=7 Hz), 2.04 (2H, qui, J=7 Hz)
(CDCI3); 8.05 (3H, m), 7.78 (2H, m), 7.15 (2H, d, J=9 Hz), 6.84 (2H,
106 d, J=9 Hz), 3.76 (3H, s), 3.54 (2H, q, J=7 Hz), 3.14 (3H, s), 2.72 (2H, t, J=7 Hz), 2.00 (2H, qui, J=7 Hz) (CDCI3); 8.03 (3H, m), 7.79 (2H, m), 7.11 (2H, d, J=9 Hz), 6.69 (2H,
107 d, J=9 Hz), 3.54 (2H, q, J=7 Hz), 3.14 (3H, s), 2.88 (6H, s), 2.69 (2H, t, J=7 Hz), 1.99 (2H, qui, J=7 Hz)
(CDCI3); 1.62 (3H, s), 1.69 (3H, s), 1.77 (3H, s), 2.0-2.2 (4H, m), 3.15
111 (3H, s), 4.12 (2H, t, J=6 Hz), 5.11 (1H, br), 5.36 (1H, br), 7.7-8.2 (4H, m), 7.92(1H, br)
(DMSO-d6); 1.75-1.90 (2H, m), 2.54 (2H, t, J=7 Hz), 2.63 (3H, s),
135 2.83 (6H, s), 3.25-3.35 (2H, m), 6.67 (2H, d, J=9 Hz), 7.06 (2H, d, J=9 Hz), 7.85-7.96 (2H, m), 8.10-8.20 (1H, m), 8.40-8.50 (1H, m), 8.87 (1H, brs)
(CDCI3); 3.17 (3H, s), 3.82 (2H, t, J=6 Hz), 4.24 (2H, t, J=6 Hz), 4.64
246 (2H, d, J=6 Hz), 6.93 (2H, d, J=9 Hz), 7.35 (2H, d, J=9 Hz), 7.7-7.9 (2H, m), 8.0-8.1 (2H, m), 8.33 (1H, br)
(DMSO-d6); 2.83 (3H, s), 4.48 (2H, d, J=6 Hz), 4.66 (2H, s), 6.91
241 (2H, d, J=9 Hz), 7.33 (2H, d, J=9 Hz), 7.8-8.0 (2H, m), 8.0-8.2 (2H, m), 9.33 (1H,t, J=6 Hz)
(CDCI3); 3.17 (3H, s), 4.61 (2H, d, J=6 Hz), 5.91 (1H, brs), 7.00 (1H,
242 d, J=8 Hz), 7.26 (1H, dd, J=2 Hz, J=8 Hz), 7.52 (1H, d, J=2 Hz), 7.7 - 7.9 (2H, m), 8.0-8.1 (2H, m), 8.40 (1H, brs)
(CDCI3); 3.17 (3H, s), 3.92 (3H, s), 4.77 (2H, d, J=6 Hz), 7.48 (2H, d,
243 J=8 Hz), 7.7-7.9 (2H, m), 8.0-8.1 (2H, m), 8.04 (2H, d, J=8 Hz), 8.51(1H, brs)
(CDCI3); 1.75 (1H, t, J=6 Hz), 4.70 (4H, d, J=6 Hz), 7.3-7.5 (4H, m),
244 7.7-7.9 (2H, m), 8.0-8.1 (2H, m), 8.39 (1H, brs)
Using the suitable starting compounds, there are obtained the compounds as listed in Table 6 in the same manner as in Examples 1 to 4. Table 6
Figure imgf000382_0001
Example 247 Structure:
Figure imgf000382_0002
R1: H R2: CH3 m: 1 n: 0 r:
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethanol
M.p. (°C): 206-208
Form: Free
Example 248 Structure:
Figure imgf000382_0003
H C m: 1 n: 0 r: 1
Crystalline form: White powder Solvent for recrystal.: Ethanol M.p. (°C): 142-144 Form: Free Example 249 Structure: NHCOCH3
Figure imgf000383_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 213-214
Form: Free
Example 250 Structure:
Figure imgf000383_0002
Crystalline form: Colorless granules
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 160-162
Form: Free
Example 251 Structure:
Figure imgf000383_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale brown powder M.p. (°C): 235-236 (decomposed) Form: Free Example 252 Structure:
Figure imgf000384_0001
Crystalline form: Pale brown powder
Solvent for recrystal.: Ethanol
M.p. (°C): 198-200
Form: Free
Example 253 Structure:
Figure imgf000384_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: 2-Propanol
M.p. (°C): 140-141
Form: Free
Example 254 Structure:
Figure imgf000384_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 185-190
Form: Free Example 255 Structure:
Figure imgf000385_0001
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 197-198
Form: Free
Example 256 Structure:
Figure imgf000385_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow granules
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 255-256 (decomposed)
Form: Free
Example 257 Structure:
Figure imgf000385_0003
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethanol
M.p. (°C): 230-231 (decomposed)
Form: Free Example 258 Structure:
Figure imgf000386_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale brown powder
Solvent for recrystal.: Ethanol
M.p. (°C): 142-146
Form: Free
Example 259 Structure:
Figure imgf000386_0002
R1: H R2 : CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Ethanol/water
M.p. (°C): 227-228
Form: Free
Example 260 Structure:
Figure imgf000386_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 248-250 (decomposed)
Form: Free Example 261 Structure:
Figure imgf000387_0001
Crystalline form: White powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 234-236 Form: Free
Example 262 Structure:
Figure imgf000387_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 193-194
Form: Free
Example 263 Structure:
Figure imgf000387_0003
Crystalline form: White powder Solvent for recrystal.: Ethanol M.p. (°C): 166-167 Form: Free Example 264 Structure:
Figure imgf000388_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder Solvent for recrystal.: Acetonitrile M.p. (°C): 212-213 Form: Free
Example 265 Structure:
Figure imgf000388_0002
H3
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder Solvent for recrystal.: Ethanol M.p. (°C): 246-247 (decomposed) Form: Free
Example 266 Structure:
Figure imgf000388_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 197-198 Form: Free Example 267 Structure:
Figure imgf000389_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow amorphous Form: Free
Example 268 Structure:
Figure imgf000389_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Acetonitrile
M.p. (°C): 235-236 (decomposed)
Form: Free
Example 269 Structure:
Figure imgf000389_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 143-147
Form: Free Example 270 Structure:
Figure imgf000390_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 175-177
Form: Free
Example 271 Structure:
Figure imgf000390_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Acetonitrile
M.p. (°C): 226-227
Form: Free
Example 272 Structure:
Figure imgf000390_0003
R1: H R2: CH3 m: 1 n: 0 r:
Crystalline form: Pale yellow granules
Solvent for recrystal.: Ethanol
M.p. (°C): 139-144
Form: Free Example 273 Structure:
Figure imgf000391_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow granules
Solvent for recrystal.: Ethanol
M.p. (°C): 184-187
Form: Free
Example 274 Structure:
Figure imgf000391_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 183-185
Form: Free
Example 275 Structure:
Figure imgf000391_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Diethyl ether
M.p. (°C): 118-120
Form: Free Example 276 Structure:
Figure imgf000392_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 217-218 Form: Free
Example 277 Structure:
Figure imgf000392_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 213-214 Form: Free
Example 278 Structure:
Figure imgf000392_0003
W: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless prisms Solvent for recrystal.: Ethanol M.p. (°C): 138-140 Form: Free Example 279 Structure:
Figure imgf000393_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 121 -122
Form: Free
Example 280 Structure:
Figure imgf000393_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 247-248 Form: Free
Example 281 Structure:
Figure imgf000393_0003
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: Ethanol
M.p. (°C): 178-180
Form: Free Example 282 Structure:
Figure imgf000394_0001
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless granules
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 190-191
Form: Free
Example 283 Structure:
Figure imgf000394_0002
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder Solvent for recrystal.: Ethyl acetate M.p. (°C): 238-240 (decomposed) Form: Free
Example 284 Structure:
Figure imgf000394_0003
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 221-222 Form: Free Example 285 Structure:
Figure imgf000395_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 137-138
Form: Free
Example 286 Structure:
Figure imgf000395_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 144-145
Form: Free
Example 287 Structure:
Figure imgf000395_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 70-73
Form: Free Example 288 Structure:
Figure imgf000396_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 189-190
Form: Free
Example 289 Structure:
Figure imgf000396_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 145-147
Form: Free
Example 290 Structure:
Figure imgf000396_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 134-135 Form: Free Example 291 Structure:
Figure imgf000397_0001
R '\ H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless granules
Solvent for recrystal.: Ethanol
M.p. (°C): 174-176
Form: Free
Example 292 Structure:
Figure imgf000397_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 160-162
Form: Free
Example 293 Structure:
Figure imgf000397_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 196-197
Form: Free Example 294 Structure:
: - °C-NHCHs
Figure imgf000398_0001
Figure imgf000398_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 156-160
Form: Free
Example 295 Structure:
Figure imgf000398_0003
R-: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
M.p. (°C): 129-131
Form: Free
Example 296 Structure:
Figure imgf000398_0004
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles
Solvent for recrystal.: n-Hexane/ethyl acetate
M.p. (°C): 113-115
Form: Free Example 297 Structure:
Figure imgf000399_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless granules
Solvent for recrystal.: Ethanol
M.p. (°C): 187-191
Form: Free
Example 298 Structure:
Figure imgf000399_0002
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless granules
Solvent for recrystal.: Ethanol
M.p. (°C): 145-146
Form: Free
Example 299 Structure:
Figure imgf000399_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 184-186
Form: Free Example 300 Structure:
Figure imgf000400_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 162-163 Form: Free
Example 301 Structure:
Figure imgf000400_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 179-180 Form: Free
Example 302 Structure:
Figure imgf000400_0003
R : H R2: CH3 m: 1 n: 0 r:
Crystalline form: Pale brown granules
Solvent for recrystal.: Ethanol
M.p. (°C): 120-122
Form: Free Example 303 Structure:
Figure imgf000401_0001
Crystalline form: Pale yellow granules Solvent for recrystal.: Ethanol M.p. (°C): 103-105 Form: Free
Example 304 Structure:
H3C
— fiC-N A : - ?C.-NHCH2 OϊC ^^ 0(CH2)2OC2H5
R4
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 123-125
Form: Free
Example 305 Structure:
Figure imgf000401_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder Form: Free Example 306 Structure:
Figure imgf000402_0001
W: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Form: Free
Example 307 Structure:
Figure imgf000402_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Diethyl ether
M.p. (°C): 103-105
Form: Free
Example 308 Structure:
Figure imgf000402_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Ethanol
M.p. (°C): 191-193
Form: Free Example 309 Structure:
Figure imgf000403_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 141.5-143
Form: Free
Example 310 Structure:
Figure imgf000403_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow prisms
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 162-163
Form: Free
Example 311 Structure:
Figure imgf000403_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow prisms
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 178-179
Form: Free Example 312 Structure:
Figure imgf000404_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethanol
M.p. (°C): 230-231
Form: Free
Example 313 Structure:
Figure imgf000404_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Ethanol
M.p. (°C): 124.5-125
Form: Free
Example 314 Structure: H3
Figure imgf000404_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Dichloromethane/diethyl ether
M.p. (°C): 198-200
Form: Free Example 315 Structure:
— BC-N A : - °C-NHCH2CH=C jgαc"' X R4 CH3
R-: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/ethanol
Form: Free
Example 316 Structure:
Figure imgf000405_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/ethanol
M.p. (°C): 193.5-196
Form: Free
Example 317 Structure:
Figure imgf000405_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White flakes
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 203.5-207.5
Form: Free Example 318 Structure:
Figure imgf000406_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder Solvent for recrystal.: Dichloromethane/n-hexane M.p. (°C): 162-163 Form: Free
Example 319 Structure:
Figure imgf000406_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 191-193
Form: Free
Example 320 Structure:
Figure imgf000406_0003
3
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles Solvent for recrystal.: Dichloromethane/n-hexane M.p. (°C): 119-120 Form: Free Example 321 Structure:
Figure imgf000407_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow flakes
Solvent for recrystal.: Dichloromethane/diethyl ether
M.p. (°C): 86-88
Form: Free
Example 322 Structure:
Figure imgf000407_0002
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White flakes
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 140-142
Form: Free
Example 323 Structure:
Figure imgf000407_0003
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 115-117
Form: Free Example 324 Structure:
Figure imgf000408_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 129-133
Form: Free
Example 325 Structure:
Figure imgf000408_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/diethyl ether
M.p. (°C): 177-179
Form: Free
Example 326 Structure:
Figure imgf000408_0003
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 144-146
Form: Free Example 327 Structure:
Figure imgf000409_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Form: Free
Example 328 Structure:
Figure imgf000409_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White amorphous Form: Free
Example 329 Structure:
Figure imgf000409_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 173-174
Form: Free Example 330 Structure:
Figure imgf000410_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 173-175
Form: Free
Example 331 Structure:
Figure imgf000410_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 193-196
Form: Free
Example 332 Structure:
Figure imgf000410_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 100-101
Form: Free Example 333 Structure:
Figure imgf000411_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 151-152
Form: Free
Example 334 Structure:
Figure imgf000411_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 141 -142
Form: Free
Example 335 Structure:
— fiC-N
Figure imgf000411_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White amorphous Form: Free Example 336 Structure:
Figure imgf000412_0001
Crystalline form: White needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 143.5-145
Form: Free
Example 337 Structure:
Figure imgf000412_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder Solvent for recrystal.: Dichloromethane/n-hexane M.p. (°C): 217-219 Form: Free
Example 338 Structure:
Figure imgf000412_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale brown powder
Solvent for recrystal.: Ethanol
M.p. (°C): 166-168
Form: Free Example 339 Structure:
Figure imgf000413_0001
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 223-228
Form: Free
Example 340 Structure:
Figure imgf000413_0002
R1; H R2: CH. i m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Dichloromethane/diethyl ether
M.p. (°C): 228-230
Form: Free
Example 341 Structure:
Figure imgf000413_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 150-151
Form: Free Example 342 Structure:
/
-C-N -C-NHCH2CH
\ ■ S &
CH3
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder Solvent for recrystal.: Ethanol M.p. (°C): 237-239 Form: Free
Example 343 Structure:
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 180-205
Form: Free
Example 344 Structure:
Figure imgf000414_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Methanol/dichloromethane/n-hexane
M.p. (°C): 240-243
Form: Free Example 345 Structure:
H
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White flakes
Solvent for recrystal.: Methanol/dichloromethane/n-hexane
M.p. (°C): 182.5-186
Form: Free
Example 346 Structure:
Figure imgf000415_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow amorphous Form: Free
Example 347 Structure:
Figure imgf000415_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White amorphous Form: Free Example 348 Structure:
Figure imgf000416_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow oil
Form: Free
Example 349 Structure:
Figure imgf000416_0002
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White flakes
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 178.5-180
Form: Free
Example 350 Structure:
Figure imgf000416_0003
R1; H R2: -CH2F m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 153-155
Form: Free Example 351 Structure:
Figure imgf000417_0001
R> H R2: -CH2F m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 126-131
Form: Free
Example 352 Structure:
Figure imgf000417_0002
R1: H R2: -CH2F m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 111 -114
Form: Free
Example 353 Structure:
Figure imgf000417_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless oil
Form: Free Example 354 Structure:
0C0CH3
Figure imgf000418_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow amorphous Form: Free
Example 355 Structure:
Figure imgf000418_0002
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow amorphous Form: Free
Example 356 Structure:
Figure imgf000418_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 124.5-128
Form: Free Example 357 Structure:
Figure imgf000419_0001
Crystalline form: White powder
Solvent for recrystal.: Dichloromethane/n-hexane
M.p. (°C): 129-132
Form: Free
Example 358 Structure:
Figure imgf000419_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White needles
Solvent for recrystal.: Dichioromethane/n-hexane
M.p. (°C): 149-150
Form: Free
Example 359 Structure:
Figure imgf000419_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 151 -153
Form: Free Example 360 Structure:
Figure imgf000420_0001
OCH3
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 237-238
Form: Free
Example 361 Structure:
Figure imgf000420_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow flakes
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 160-161
Form: Free
Example 362 Structure:
Figure imgf000420_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 169-170
Form: Free Example 363 Structure:
Figure imgf000421_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 190-191
Form: Free
Example 364 Structure:
Figure imgf000421_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 180-181
Form: Free
Example 365 Structure:
Figure imgf000421_0003
R1: H R2: CH3 m: 1 n: 0 r:
Crystalline form: Coloriess granules
Solvent for recrystal.: Acetone
M.p. (°C): 173-174
Form: Free Example 366 Structure:
Figure imgf000422_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 203-204
Form: Free
Example 367 Structure: OCH3
Figure imgf000422_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 250-251
Form: Free
Example 368 Structure: , NHCOCH3
Figure imgf000422_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 246-247
Form: Free Example 369 Structure:
Figure imgf000423_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 247-248
Form: Free
Example 370 Structure:
Figure imgf000423_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 160-161
Form: Free
Example 371 Structure:
Figure imgf000423_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale brown prisms
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 214-215
Form: Free Example 372 Structure:
0
Figure imgf000424_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess prisms
Solvent for recrystal.: Acetone
M.p. (°C): 202-203
Form: Free
Example 373 Structure:
Figure imgf000424_0002
R -: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Methanol
M.p. (°C): 254-255
Form: Free
Example 374 Structure:
Figure imgf000424_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 201-203
Form: Free Example 375 Structure:
Figure imgf000425_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 161-162
Form: Free
Example 376 Structure:
Figure imgf000425_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 197-198
Form: Free
Example 377 Structure:
Figure imgf000425_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 171 -172
Form: Free Example 378 Structure:
Figure imgf000426_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 108-109
Form: Free
Example 379 Structure:
Figure imgf000426_0002
R H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 117-120
Form: Free
Example 380 Structure:
Figure imgf000426_0003
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow amorphous
M.p. (°C): 97-100
Form: Free Example 381 Structure:
Figure imgf000427_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 148-149 Form: Free
Example 382 Structure:
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Acetone/n-hexane
M.p. (°C): 156-157
Form: Free
Example 383 Structure:
Figure imgf000427_0003
Crystalline form: Yellow granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 159-160
Form: Free Example 384 Structure:
Figure imgf000428_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Acetone/n-hexane
M.p. (°C): 177-178
Form: Free
Example 385 Structure:
Figure imgf000428_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 181-182
Form: Free
Example 386 Structure:
Figure imgf000428_0003
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 196-197
Form: Free Example 387 Structure:
Figure imgf000429_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 186-187
Form: Free
Example 388 Structure:
Figure imgf000429_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Chloroform/n-hexane
M.p. (°C): 175-176
Form: Free
Example 389 Structure:
Figure imgf000429_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles Solvent for recrystal.: Ethyl acetate M.p. (°C): " 136-138 Form: Free Example 390 Structure:
Figure imgf000430_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 173-174
Form: Free
Example 391 Structure:
C- F3
Figure imgf000430_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless flakes
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 186-187
Form: Free
Example 392 Structure:
Figure imgf000430_0003
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow flakes
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 197-198
Form: Free Example 393 Structure:
Figure imgf000431_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow flakes
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 230-231
Form: Free
Example 394 Structure:
Figure imgf000431_0002
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 225-226
Form: Free
Example 395 Structure:
Figure imgf000431_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 196-197
Form: Free Example 396 Structure:
Figure imgf000432_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 160-161 Form: Free
Example 397 Structure:
Figure imgf000432_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 218-220 (decomposed)
Form: Free
Example 398 Structure:
Figure imgf000432_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 168-169
Form: Free Example 399 Structure:
Figure imgf000433_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow prisms Solvent for recrystal.: Ethanol M.p. (°C): 202-203 Form: Free
Example 400 Structure:
Figure imgf000433_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles Solvent for recrystal.: Ethyl acetate M.p. (°C): 159-160 Form: Free
Example 401 Structure:
Figure imgf000433_0003
R1: 6- and 7-CH3 R2: CH3 m: 1 n: 0 r: 2
Crystalline form: Brown needles
Solvent for recrystal.: Chloroform/n-hexane
M.p. (°C): 207-208
Form: Free Example 402 Structure:
Figure imgf000434_0001
R1: 6- and 7-CH3 R2: CH3 m: 1 n: 0 r: 2
Crystalline form: Brown flakes
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 189-190
Form: Free
Example 403 Structure:
Figure imgf000434_0002
R-: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Form: Free
Example 404 Structure:
Figure imgf000434_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Form: Free Example 405 Structure:
Figure imgf000435_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Orange powder Form: Free
Example 406 Structure:
Figure imgf000435_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Orange powder Form: Free
Example 407 Structure:
Figure imgf000435_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder Form: Free Example 408 Structure:
Figure imgf000436_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder Form: Free
Example 409 Structure:
Figure imgf000436_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Brown prisms Solvent for recrystal.: Ethanol/dimethylformamide M.p. (°C): 179-180 Form: Free
Example 410 Structure:
Figure imgf000436_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow prisms
Solvent for recrystal.: Ethanol/dimethylformamide
M.p. (°C): 231-233
Form: Free Example 411 Structure:
Figure imgf000437_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 203-204
Form: Free
Example 412 Structure:
Figure imgf000437_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 129-130
Form: Free
Example 413 Structure:
Figure imgf000437_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow prisms
Solvent for recrystal.: Ethanol
M.p. (°C): 177-178
Form: Free Example 414 Structure:
Figure imgf000438_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Ethanol
M.p. (°C): 120-122
Form: Free
Example 415 Structure:
Figure imgf000438_0002
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 142-143 Form: Free
Example 416 Structure:
Figure imgf000438_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethanol/dimethylformamide
M.p. (°C): 189-190
Form: Free Example 417 Structure:
Figure imgf000439_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Dimethylformamide
M.p. (°C): 236-237
Form: Free
Example 418 Structure:
Figure imgf000439_0002
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow prisms
Solvent for recrystal.: Dimethylformamide
M.p. (°C): 229-230
Form: Free
Example 419 Structure:
Figure imgf000439_0003
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Ethanol/dimethylformamide
M.p. (°C): 233-234
Form: Free Example 420 Structure:
Figure imgf000440_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Brown plates
Solvent for recrystal.: Ethanol/dimethylformamide
M.p. (°C): 196-197
Form: Free
Example 421 Structure:
Figure imgf000440_0002
Crystalline form: Yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 163-165
Form: Free
Example 422 Structure:
Figure imgf000440_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethanol
M.p. (°C): 213-214
Form: Free Example 423 Structure:
Figure imgf000441_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Ethanol/dimethylformamide
M.p. (°C): 220-221
Form: Free
Example 424 Structure:
Figure imgf000441_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Dimethylformamide
M.p. (°C): 214-215
Form: Free Example 425 Structure:
o RJ o
11 / II
—C-N : -C-NHCH2 jgCCf'
Y4
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder Solvent for recrystal.: Dimethylformamide M.p. (°C): 244 (decomposed) Form: Free
Example 426 Structure:
Figure imgf000442_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 186-188
Form: Free
Example 427 Structure:
Figure imgf000442_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 174-175
Form: Free Example 428 Structure:
Figure imgf000443_0001
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow powder
Solvent for recrystal.: Dimethylformamide
M.p. (°C): 202-203
Form: Free
Example 429 Structure:
Figure imgf000443_0002
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 167-168 Form: Free
Example 430 Structure:
Figure imgf000443_0003
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder Solvent for recrystal.: Ethanol M.p. (°C): 174-175 Form: Free Example 431 Structure:
Figure imgf000444_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 209-210
Form: Free
Example 432 Structure:
Figure imgf000444_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
M.p. (°C): 198-199
Form: Free
Example 433 Structure:
Figure imgf000444_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Dimethylformamide
M.p. (°C): 91-93
Form: Free Example 434 Structure:
Figure imgf000445_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: Ethanol
M.p. (°C): 212-213
Form: Free
Example 435 Structure:
Figure imgf000445_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess prisms Solvent for recrystal.: Dimethylformamide M.p. (°C): 237-238 (decomposed) Form: Free
Example 436 Structure:
Figure imgf000445_0003
Crystalline form: Pale yellow needles Solvent for recrystal.: Dimethylformamide/ethanol M.p. (°C): 209-209.5 Form: Free Example 437 Structure:
Figure imgf000446_0001
R1; H R2: CH3 m: 1 n: 0 r. 1
Crystalline form: Colorless needles Solvent for recrystal.: Ethanol M.p. (°C): 198.5-199 Form: Free
Example 438 Structure:
Figure imgf000446_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethanol
M.p. (°C): 193.5-194
Form: Free
Example 439 Structure:
Figure imgf000446_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
M.p. (°C): 211
Form: Free Example 440 Structure:
Figure imgf000447_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles Solvent for recrystal.: Ethanol M.p. (°C): 137-138 Form: Free
Example 441 Structure:
—C π-N / -C-NHCH2CH=C J.θQ
\ CH3
R1: H R2: CH3 m: 0 n: 0 r: 1
Crystalline form: Coloriess needles Solvent for recrystal.: Ethanol M.p. (°C): 155.5-156 Form: Free
Example 442 Structure:
Figure imgf000447_0002
R1: H R2: CH3 m: 1 n: 1 r: 1
Crystalline form: Pale yellow prisms Solvent for recrystal.: Ethanol M.p. (°C): 219-220 Form: Free Example 443 Structure:
Figure imgf000448_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 117-118
Form: Free
Example 444 Structure:
Figure imgf000448_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Diethyl ether/n-hexane
M.p. (°C): 127-129
Form: Free
Example 445 Structure:
Figure imgf000448_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 212-213 (decomposed)
Form: Free Example 446 Structure:
Figure imgf000449_0001
R1 : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 197-198
Form: Free
Example 447 Structure:
Figure imgf000449_0002
R1 : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 198-199
Form: Free
Example 448 Structure:
Figure imgf000449_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules Solvent for recrystal.: Ethanol I M.p. (°C): 155-156 Form: Free
Figure imgf000450_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Diethyl ether
M.p. (°C): 100-105
Form: Free
Example 450 Structure:
Figure imgf000450_0002
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles
Solvent for recrystal.: Ethanol
M.p. (°C): 215-216 (decomposed)
Form: Free
Example 451 Structure:
Figure imgf000450_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess granules
Solvent for recrystal.: Diethyl ether
M.p. (°C): 103-105
Form: Free Example 452 Structure:
Figure imgf000451_0001
R -: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow granules
Solvent for recrystal.: Diethyl ether
M.p. (°C): 124-126
Form: Free
Example 453 Structure:
Figure imgf000451_0002
R1: H R2: CH3 m: 1 n: 0
Crystalline form: Pale yellow granules
Solvent for recrystal.: Diethyl ether
M.p. (°C): 124-125
Form: Free
Example 454 Structure:
Figure imgf000451_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: White powder
Solvent for recrystal.: n-Hexane/diethyl ether
M.p. (°C): 119-121
Form: Free Example 455 Structure:
Figure imgf000452_0001
R -\ H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow granules
Solvent for recrystal.: Diethyl ether
M.p. (°C): 100-101
Form: Free
Example 456 Structure:
Figure imgf000452_0002
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow powder
Solvent for recrystal.: Diethyl ether
M.p. (°C): 122-124
Form: Free
Example 457 Structure:
Figure imgf000452_0003
Crystalline form: White powder
Solvent for recrystal.: Diethyl ether
M.p. (°C): 107-109
Form: Free Example 458 Structure:
Figure imgf000453_0001
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Red powder Form: Free
Example 459 Structure:
Figure imgf000453_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 125-129
Form: Free
Example 460 Structure:
Figure imgf000453_0003
R1: H R2: CH3 m: 1 n: 0 r:
Crystalline form: Pale yellow needles
Solvent for recrystal.: Ethanol
M.p. (°C): 154-157
Form: Free Example 461 Structure:
Figure imgf000454_0001
Crystalline form: Pale yellow needles
Solvent for recrystal.: Dichloromethane/ethanol
M.p. (°C): 206-208
Form: Free
Example 462 Structure:
Figure imgf000454_0002
Crystalline form: Pale yellow needles Solvent for recrystal.: Dichloromethane/ethanol M.p. (°C): 205-208 Form: Free
Example 463 Structure:
Figure imgf000454_0003
R1: 7-OCH3 R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Brown granules
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 196-197
Form: Free Example 464 Structure:
Figure imgf000455_0001
R : 7-N(C2H5)2 R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Red needles
Solvent for recrystal.: Ethyl acetate
M.p. (°C): 202-204
Form: Free
Example 465 Structure:
Figure imgf000455_0002
R1: 6-CON(C2H5)2 R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Isopropanol
M.p. (°C): 160-162
Form: Free
Example 466 Structure:
Figure imgf000455_0003
R1; H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 172-173
Form: Free Example 467 Structure:
Figure imgf000456_0001
Crystalline form: Yellow granules Solvent for recrystal.: Ethanol/water M.p. (°C): 141-142 Form: Free
Example 468 Structure:
Figure imgf000456_0002
R : H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow plates
Solvent for recrystal.: Acetone/n-hexane
M.p. (°C): 148-150
Form: Free
Example 469 Structure:
Figure imgf000456_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow granules
Solvent for recrystal.: Acetonitrile
M.p. (°C): 221-223
Form: Free Example 470 Structure:
Figure imgf000457_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Acetonitrile
M.p. (°C): 207-208
Form: Free
Example 471 Structure:
Figure imgf000457_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Dimethylformamide/water
M.p. (°C): 205-206
Form: Free
Example 472
Structure:
Figure imgf000457_0003
R -: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 171 -172 Form: Free Example 473 Structure:
Figure imgf000458_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles Solvent for recrystal.: Ethyl acetate/n-hexane M.p. (°C): 179-180 Form: Free
Example 474 Structure:
Figure imgf000458_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless needles Solvent for recrystal.: Acetonitrile M.p. (°C): 188-189 Form: Free
Example 475 Structure:
Figure imgf000459_0001
R"": H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Coloriess needles
Solvent for recrystal.: Acetonitrile/water
M.p. (°C): 174-175
Form: Free
Example 476 Structure:
Figure imgf000459_0002
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 187-188
Form: Free
Example 477 Structure:
Figure imgf000459_0003
Crystalline form: Coloriess needles
Solvent for recrystal.: Ethyl acetate/n-hexane
M.p. (°C): 183-184
Form: Free Example 478 Structure:
Figure imgf000460_0001
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow needles
Solvent for recrystal.: Ethyl acetate/diisopropyl ether
M.p. (°C): 181-182
Form: Free
Example 479 Structure:
Figure imgf000460_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Pale yellow needles
Solvent for recrystal.: Diethyl ether
M.p. (°C): 109.5-110.5
Form: Free
NMR analysis:
Ex. No. 1H-NMRδppm:
(CDCI3, 250 MHz): 2.75 (6H, s), 3.08 (3H, s), 4.78 (2H, s), 4.80 (2H,
267 d, J=8 Hz), 6.67 (1H, s), 7.14 (1H, d, J=9 Hz), 7.15-7.20 (5H, m), 7.35 (1H, d, J=9 Hz), 7.45 (1H, s), 7.75-7.90 (2H, m), 8.10 (1H, m), 8.45 - 8.60 (2H, m)
(DMSO-d6, 250 MHz): 2.69 (3H, s), 4.72 (2H, d, J=6 Hz), 6.51 (1H, d,
305 J=16 Hz), 6.88 (1H, s), 7.55-7.75 (3H, m), 7.85-8.00 (3H, m), 8.16 (1H, m), 8.50 (1H, m), 9.58 (1H, t, J=6 Hz)
(DMSO-d6, 250 MHz): 2.65 (3H, s), 4.69 (2H, d, J=6 Hz), 7.68 (1H, d,
306 J=9 Hz), 7.80-8.00 (3H, m), 8.12 (1H, s), 8.15 (1H, m), 8.45 (1H, m), 8.55 (1H, s), 9.49 (1H, t, J=6 Hz), 12.91 (1H, br)
(CDCI3, 250 MHz): 2.17 (3H, s), 2.42 (3H, s), 3.11 (3H, s), 4.39 (2H, t,
315 J=7 Hz), 6.47 (1H, t, J=8 Hz), 6.62 (1H, s), 7.07 (1H, d, J=8 Hz), 7.28 (1H, s), 7.30 (1H, d, J=8 Hz), 7.78-7.83 (2H, m), 8.05-8.15 (2H, m), 8.60 (1H,m)
(DMSO-d6, 250 MHz): 1.99 (3H, s), 2.69 (3H, s), 4.18 (2H, t, J=7 Hz),
327 5.94 (1H, t, J=7 Hz), 7.59-7.70 (3H, m), 7.83 (1H, s), 7.89-7.95 (2H, m), 8.18 (1H, m), 8.48 (1H, m), 9.17 (1H, t, J=7 Hz)
(CDCI3, 250 MHz): 1.29 (6H, br), 2.25 (3H, s), 3.11 (3H, s), 3.60 (4H,
328 br), 4.34 (2H, t, J=7 Hz), 5.93 (1H, t, J=7 Hz), 7.30 (1H, s), 7.48 (2H, s), 7.68 (1H, s), 7.79-7.83 (2H, m), 8.05-8.15 (2H, m), 8.62 (1H, m)
(CDCI3> 250 MHz): 3.00 (3H, s), 3.17 (2H, t, J=7 Hz), 3.71 (2H, q, J=7
335 Hz), 3.85 (3H, s), 6.90 (1H, d, J=8 Hz), 6.92 (1H, d, J=8 Hz), 7.27 - 7.36 (2H, m), 7.70-7.81 (2H, m), 7.97 (1H, m), 8.27 (1H, brt, J=7 Hz), 8.55 (1H,m), 9.3(1 H, br)
(CDCI3, 250 MHz): 2.57 (3H, s), 3.11 (3H, s), 3.51 (3H, s), 4.85 (2H,
343 d, J=6 Hz), 5.34 (2H, s), 7.17 (1H, d, J=8 Hz), 7.29 (1H, dd, J=8 Hz, 2.5 Hz), 7.78-7.82 (2H, m), 8.06 (1H, m), 8.28 (1H, br), 8.36 (1H, d, J=2.5 Hz), 8.60(1 H.m) (CDCI3, 250 MHz): 2.17 (3H, s), 3.09 (3H, s), 3.63-3.69 (8H, m), 4.31
346 (2H, t, J=7 Hz), 4.71 (2H, s), 5.92 (1H, t, J=7 Hz), 6.85 (1H, dd, J=8 Hz, 2 Hz), 7.02 (1H, t, J=2 Hz), 7.08 (1H, d, J=8 Hz), 7.26 (1H, t, J=8 Hz), 7.76-7.83 (2H, m), 8.05-8.12 (2H, m), 8.58 (1H, m)
(CDCI3, 250 MHz): 1.14 (3H, t, J=7 Hz), 1.22 (3H, t, J=7 Hz), 2.17
347 (3H, s), 3.10 (3H, s), 3.40 (4H, q, J=7 Hz), 4.31 (2H, t, J=7 Hz), 4.69 (2H, s), 5.92 (1H, t, J=7 Hz), 6.86 (1H, d, J=8 Hz), 7.05 (1H, s), 7.06 (1H, d, J=8 Hz), 7.25 (1H, t, J=8 Hz), 7.79-7.83 (2H, m), 8.08-8.12 (2H,m), 8.60(1H,m)
(CDCI3, 250 MHz): 1.83 (3H, s), 2.18 (3H, s), 3.10 (3H, s), 4.31 (2H, t,
348 J=7 Hz), 4.45 (2H, s), 4.99 (1H, s), 5.10 (1H, s), 5.93 (1H, t, J=7 Hz), 6.84 (1H, d, J=8 Hz), 7.00 (1H, s), 7.03 (1H, d, J=8 Hz), 7.24 (1H, t, J=8 Hz), 7.78-7.82 (2H, m), 8.07-8.11 (2H, m), 8.60 (1H, m)
(CDCI3, 250 MHz): 2.18 (3H, s), 3.10 (3H, s), 3.49 (3H, s), 4.31 (2H, t,
353 J=7 Hz), 5.19 (2H, s), 5.93 (1H, t, J=7 Hz), 6.95 (1H, d, J=8 Hz), 7.08 (1H, d, J=8 Hz), 7.10 (1H, s), 7.25 (1H, t, J=8 Hz), 7.77-7.84 (2H, m), 8.06-8.11 (2H, m), 8.60(1H,m)
(CDCI3, 250 MHz): 0.87 (3H, t, J=7 Hz), 1.78-2.05 (2H, m), 2.06 (3H,
354 s), 3.10 (3H, s), 4.82 (2H, d, J=6 Hz), 5.72 (1H, t, J=8 Hz), 6.72 (1H, s), 7.26 (1H, dd, J=8 Hz, 2 Hz), 7.44 (1H, d, J=8 Hz), 7.52 (1H, d, J=2 Hz), 7.77-7.83 (2H, m), 8.08 (1H, m), 8.48 (1H, br), 8.58 (1H, m)
(CDCI3, 250 MHz): 0.91 (3H, t, J=7 Hz), 1.82 (2H, m), 3.10 (3H, s),
355 4.69 (1H, br), 4.82 (2H, d, J=6 Hz), 6.71 (1H, s), 7.25 (1H, d, J=8 Hz), 7.41 (1H, d, J=8 Hz), 7.51 (1H, s), 7.78-7.82 (2H, m), 8.07 (1H, m), 8.51 (1H, br), 8.58(1H,m)
(CDCI3, 250 MHz): 3.09 (3H, s), 3.41 (3H, s), 4.89 (2H, d, J=7 Hz),
357 7.06 (1H, d, J=2 Hz), 7.14 (1H, dd, J=8 Hz, 2 Hz), 7.43 (1H, d, J=8 Hz), 7.75-7.82 (2H, m), 8.07 (1H, m), 8.53-8.59 (2H, m)
(CDCI3, 250 MHz): 3.07 (3H, s), 3.35 (3H, s), 4.82 (2H, d, J=7 Hz),
358 6.68 (1H, s), 7.03 (1H, dd, J=8 Hz, 2 Hz), 7.17 (1H, d, J=2 Hz), 7.41 (1H, d, J=8 Hz), 7.74-7.82 (2H, m), 8.06 (1H, m), 8.52-8.57 (2H, m)
Figure imgf000463_0001
Mixture of rotamers
456 (CDCI3): 1.70, 2.20 (3H, s), 2.66 (3H, s), 3.22, 3.55 (3H, s), 4.19, 4.58 (2H, d, J=7 Hz), 4.68, 5.12 (2H, s), 6.43, 6.51 (1 H, t, J=7 Hz), 6.55, 6.70 (1H, s), 7.13-7.30 (2H, m), 7.40-7.60 (2H, m), 7.70-7.85 (2H, m), 8.10 (1 H, m), 8.60 (1 H, m)
Mixture of rotamers
457 (CDCI3): 1.74, 2.20 (3H, s), 2.00, 2.17 (3H, s), 2.66, 2.67 (3H, s), 4.29, 4.59 (2H, d, J=7 Hz), 5.42, 5.71 (2H, s), 6.35, 6.49 (1 H, t, J=7 Hz), 6.58, 6.71 (1 H, s), 7.16-7.33 (2H, m), 7.40-7.60 (2H, m), 7.75 - 7.86 (2H, m), 8.07 (1 H, m), 8.61 (1 H, m)
(DMSO-d6): 2.14 (3H, s), 2.70 (3H, s), 4.23 (2H, t, J=6 Hz), 6.43 (1 H,
458 t, J=6 Hz), 7.08 (1 H, s), 7.63 (1 H, d, J=9 Hz), 7.80-8.00 (3H, m), 8.20 (1H, m), 8.23 (1H, s), 8.48 (1H, m), 9.26 (1H, br)
Mixture of rotamers
479 (CDCI3): 1.23, 1.33 (3H, t, J=7.0 Hz), 1.74, 2.21 (3H, brs), 2.66, 2.67 (3H, s), 4.08, 4.25 (2H, q, J=7.0 Hz), 4.30, 4.62 (2H, d, J=7.5 Hz), 5.48, 5.75 (2H, s), 6.36, 6.49 (1 H, t, J=7.5 Hz), 6.57, 6.71 (1H, s), 7.15-7.35 (2H, m), 7.4-7.6 (2H, m), 7.75-7.85 (2H, m), 8.05-8.15 (1 H, m), 8.55-8.65 (1H, m)
Example 480
2-{[3-Methyl-3-(benzofuran-2-yl)-2-propenyl]aminocarbonyl}-3 - methylquinoxalin-4-oxide (0.6 g) is dissolved in methylene chloride (40 ml), and thereto are added 4-dimethylaminopyridine (0.5 g) and di-t-butyl dicarbonate (0.6 g). The mixture is stirred at room temperature for one day. The reaction solution is washed with diluted hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; n-hexane : ethyl acetate = 3 : 1), and recrystallized from n - hexane/diethyl ether to give 2-{N-t-butoxycarbonyl-N-[3-methyl-3-(benzofuran - 2-yl)-2-propenyl]aminocarbonyl}-3-methylquinoxalin-4-oxide (0.6 g) as white powder. M.p. 119-121 °C
Using the suitable starting compounds, there are obtained the compounds of Examples 443, 444, 451-453 in the same manner as in Example 480. Example 481
2-{[3-Methyl-3-(benzofuran-2-yl)-2-propenyl]aminocarbonyl}-3 - methylquinoxalin-4-oxide (1.0 g) is suspended in tetrahydrofuran (50 ml), and thereto is added sodium hydride (180 mg) under argon atmosphere. The mixture is stirred at room temperature for 40 minutes. To the mixture is added dropwise ethyl chloroformate (440 mg) under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction solution is poured into ice - water, and extracted with dichloromethane. The extract is washed with water and saturated brine solution, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; methylene chloride : methanol =
400 : 1), and recrystallized from diethyl ether to give 2-{N-ethoxycarbonyl-N-[3 - methyl-3-(benzofuran-2-yl)-2-propenyl]aminocarbonyl}-3-methylquinoxalin-4 - oxide (0.77 g) as pale yellow granules. M.p. 124-125°C Using the suitable starting compounds, there are obtained the compounds of Examples 443, 444, 451 , 452 and 454 in the same manner as in Example 481.
Example 482
2-{[3-Methyl-3-(benzofuran-2-yl)-2-propenyl]aminocarbonyl}-3 - methylquinoxalin-4-oxide (1.0 g) is suspended in dimethylformamide (10 ml), and thereto is added sodium hydride (180 mg) under ice-cooling, and the mixture is stirred at room temperature for 15 minutes. To the mixture is added dropwise methoxymethyl chloride (320 mg) under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction mixture is poured into ice water, and extracted with ethyl acetate. The extract is washed with water and brine, and dried over anhydrous sodium sulfate. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; n-hexane : ethyl acetate = 4 : 1), and recrystallized from diethyl ether to give 2-{N-methoxymethyl-N-[3-methyl-3-(benzofuran-2-yl) - 2-propenyl]aminocarbonyl}-3-methylquinoxalin-4-oxide (0.23 g) in the form of a mixture of rotamers as pale yellow powder. M.p. 122-124°C 1H-NMR (CDCI3) δ ppm: 1.70, 2.20 (3H, s), 2.66 (3H, s), 3.22, 3.55 (3H, s), 4.19, 4.58 (2H, d, J=7 Hz), 4.68, 5.12 (2H, s), 6.43, 6.51 (1 H, t, J=7 Hz), 6.55, 6.70 (1H, s), 7.13-7.30 (2H, m), 7.40-7.60 (2H, m), 7.70-7.85 (2H, m), 8.10 (1 H, m), 8.60 (1 H, m)
Using the suitable starting compounds, there are obtained the compounds of Examples 443, 444, 451-455, 457 and 479 in the same manner as in Example 482.
Example 483
To a suspension of sodium hydride (92 mg) in dimethylformamide (20 ml) is added 2-{[3-methyl-3-(benzofuran-2-yl)-2-propenyl]aminocarbonyl}-3 methylquinoxalin-4-oxide (746 mg), and the mixture is stirred at room temperature for 30 minutes. To the mixture are added chloromethyl pivalate (322 μl) and a catalytic amount of tetra-n-butylammonium iodide, and the mixture is stirred for one hour. The reaction mixture is poured into water, and extracted with ethyl acetate. The extract is washed with water and brine, and dried. The resultant is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography, and recrystallized from diethyl ether/n-hexane to give 2-{N-pivaloyloxymethyl-N-[3-methyl-3-(benzofuran-2-yl) - 2-propenyl]aminocarbonyl}-3-methylquinoxalin-4-oxide (300 mg) in the form of a mixture of rotamers as pale yellow needles. M.p. 127-129°C
1H-NMR (CDCI3) δ ppm: 1.14, 1.29 (9H, s), 1.66, 2.20 (3H, brs), 2.62,
2.66 (3H, s), 4.28, 4.59 (2H, d, J=7.2 Hz), 5.45, 5.73 (2H, s), 6.38, 6.52 (1 H, t, J=7.2 Hz), 6.57, 6.71 (1 H, s), 7.15-7.35 (2H, m), 7.4-7.5 (1 H, m), 7.5-7.6 (1 H, m), 7.76-7.87 (2H, m), 8.05-8.15 (1 H, m), 8.55-8.65 (1 H, m) Using the suitable starting compounds, there are obtained the compounds of Examples 443, 451-457 and 479 in the same manner as in Example 483. Using the suitable starting compounds, there are obtained the compounds as listed in Table 7 in the same manner as in Examples 1 to 4. Table 7
Figure imgf000467_0001
Example 484 Structure:
Figure imgf000467_0002
Crystalline form: White powder Solvent for recrystal.: Diethyl ether M.p. (°C): 129-134 Form: Free
Example 485 Structure:
Figure imgf000467_0003
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Yellow granules
Solvent for recrystal.: Diethyl ether
M.p. (°C): 126-127
Form: Free Example 486 Structure:
Figure imgf000468_0001
Crystalline form: Pale yellow granules
Solvent for recrystal.: Diethyl ether
M.p. (°C): 170-172
Form: Free
Example 487 Structure:
Figure imgf000468_0002
R1: H R2: CH3 m: 1 n: 0 r: 1
Crystalline form: Colorless granules Solvent for recrystal.: Ethanol M.p. (°C): 140-141 Form: Free
Ex. No. 1H-NMR δ ppm:
Mixture of rotamers
485 (CDCI3): 1.86, 1.87 (3H, s), 2.06, 2.40 (3H, s), 2.50, 2.61 (3H, s), 4.91 , 5.08 (2H, s), 5.48, 5.71 (2H, s), 7.26-7.40 (1 H, m), 7.50-7.60 (1 H, m), 7.65-7.75 (1 H, m), 7.75-7.86 (2H, m), 7.98-8.15 (1 H, m), 8.55-8.65 (1 H, m)
Mixture of rotamers
487 (CDCI3): 1.98, 2.11 (3H, s), 2.15, 2.53 (3H, s), 2.64, 2.69 (3H, s), 4.60, 4.80 (2H, s), 5.55, 5.72 (2H, s), 7.40-7.50 (3H, m), 7.70-7.80 (2H, m), 7.85-8.10 (3H, m), 8.55-8.65 (1 H, m) Pharmacological Experiment
Experiment: Test of glucose-uptake by L6 cells
L6 cells (derived from rat striated muscle) were pre-cultured in minimum essential medium (MEM) containing 10 % FCS and put onto a 48 - well plate by each 4 x 104 cells/well. The plate was cultured in 2 % FCS so that L6 cells were differentiated into muscle cells. Six days later, a test compound was added to the culture mixture, and the culture solution was removed the following day, and further thereto was added [3H]-2-deoxyglucose, and the plate was reacted at 37°C for 10 minutes. After the reaction is complete, the plate was washed twice with cold phosphate buffer saline solution, and the cells were subjected to hydrolysis with 0.1 % sodium docecylsulfate, and the radioactivity of the resultant was measured. The glucose-uptake was estimated by comparing the radioactivity of the well with a test compound with the radioactivity of the well without a test compound (control) and expressed by percentage (%). The results are shown in Table 8.
Table 3
Test Dose Glucose - Test Dose Glucose - Comp. (mole) uptake Comp. (mole) uptake
(%) (%)
Ex. 29 10-o 201 Ex. 30 10-o 210
Ex. 33 10-o 120 Ex. 39 10-o 159
Ex. 41 10-o 181 Ex. 44 10-o 176
Ex. 45 10-o 147 Ex. 46 10-o 217
Ex. 47 10-o 148 Ex. 60 10-o 166
Ex. 61 10-o 154 Ex. 62 10-o 223
Ex. 66 10-o 154 Ex. 69 10-o 194
Ex. 73 10-o 168 Ex. 75 10-o 249
Ex. 77 10-o 245 Ex. 83 10-o 153
Ex. 85 10-o 177 Ex. 92 10-6 201
Ex. 93 10-o 240 Ex. 94 10-0 188
Ex. 96 10-o 200 Ex. 97 10-o 136
Ex. 99 10-o 154 Ex. 103 10-o 198
Ex. 105 10-0 186 Ex. 107 10-0 206
Ex. 109 10-o 222 Ex. 110 10-5 209
Ex. 112 10-0 159 Ex. 113 10-0 123
Ex. 117 10-0 226 Ex. 119 10-o 158
Ex. 122 10-0 199 Ex. 125 10-o 188
Ex. 126 10-0 212 Ex. 130 10-5 161
Ex. 132 10-0 187 Ex. 134 10-5 125
Ex. 136 10-o 129 Ex. 143 10-0 210
Ex. 145 10-0 136 Ex. 147 10-o 138
Ex. 150 10-6 203 Ex. 151 10-0 156
Ex. 148 10-0 183 Ex. 153 10-5 191
Ex. 154 10-o 163 Ex. 155 10-0 212
Ex. 156 10-o 155 Ex. 159 10-5 152 Ex.162 10-5 187 Ex.166 10-o 168
Ex.170 10-0 165 Ex.171 10-0 163
Ex.175 10-0 123 Ex.177 10-0 178
Ex.179 10-6 200 Ex.181 10-0 223
Ex.182 10-o 150 Ex.183 10-5 212
Ex.185 10-o 169 Ex.190 10-o 193
Ex.193 10-0 121 Ex.199 10-o 165
Ex.200 10-6 142 Ex.201 10-6 207
Ex.203 10-o 239 Ex.204 10-6 192
Ex.208 10-o 125 Ex.210 10-o 145
Ex.212 10-o 121 Ex.213 10-o 146
Ex.215 10-o 186 Ex.221 10-6 120
Ex.224 10-o 135 Ex.229 10-o 149
Ex.238 10-o 144 Ex.383 10-0 168
Ex.428 10-o 128 Ex.446 10-o 183
Ex.459 10-o 127 Ex.460 10-o 158
Ex.470 10-6 204

Claims

1. A quinoxaline derivative of the formula:
Figure imgf000472_0001
wherein R1 is hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent,
R2 is hydrogen atom, a lower alkyl group having optionally a halogen substituent, phenyl group, a morpholino-substituted lower alkyl group or an imidazolyl-substituted lower alkyl group, n is O, m is 0 or 1 , r is 1 or 2,
R3 and R4 are the same or different and each a) hydrogen atom; b) a lower alkyl group; c) a phenyl-lower alkoxycarbonyl group; d) a lower alkanoyloxy-substituted lower alkyl group; e) a lower alkanoyl group; f) a lower alkoxycarbonyl group; g) a lower alkoxy-lower alkyl group; h) a phenoxy - carbonyl group; i) a lower alkanoyl-substituted lower alkyl group; j) a lower alkoxycarbonyloxy-substituted lower alkyl group; k) a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring; I) a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); m) a group of the formula:
Figure imgf000473_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); n) a group of the formula:
Figure imgf000473_0002
(in which A is the same as defined above, p is an integer of 1 to 3, R5 is a lower alkoxy-substituted lower alkoxy group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, a halogen atom, nitro group, hydroxy group, a lower alkyl group having optionally a hydroxy substituent, a lower alkenyloxy group, a carboxyl-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a lower alkoxycarbonyl group, a halogen-substituted lower alkoxy group, a hydroxy-substituted lower alkoxy group, a phenyl-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety, a 1 ,3 - dioxolanyl group having optionally a lower alkyl substituent, a lower alkanoyl group, a morpholino-substituted lower alkoxy group, a morpholino-substituted lower alkyl group, a morpholinocarbonyl group or a group of the formula: -Y-ArCONR6R7 (in which Ai is a lower alkylene group, Y is a group of the formula: -O- or a group of the formula: -NH-, R6 and R7 are the same or different and each hydrogen atom, a lower alkyl group having optionally a hydroxy substituent, a phenyl-lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, a furyl-substituted lower alkyl group, or a lower alkoxy-substituted lower alkyl group, or R6 and R7 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with nitrogen atom or oxygen atom, said heterocyclic group having optionally 1 to 3 substituents selected from hydroxy group, a lower alkyl group and a phenyl - lower alkyl group)); o) a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6 - membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; p) an alkenyl group; q) a cycloalkyl-lower alkyl group; r) a naphthyl - lower alkyl group; s) a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; t) a phenylsulfinyl - substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; u) a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; v) a phenoxy - substituted lower alkyl group; w) a group of the formula:
Figure imgf000474_0001
(in which q is an integer of 1 to 3, a group of the formula: A~~
is a lower alkyl group substituted by a 5- to 14-membered saturated or unsaturated heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R8 substitutes on the above heterocyclic group, and is hydrogen atom, oxo group, a lower alkyl group having optionally a hydroxy substituent, a halogen atom, nitro group, a lower alkoxy group, cyano group, a lower alkoxycarbonyl group, a phenyl-lower alkoxy group having optionally an amino group having optionally a lower alkanoyl substituent on the phenyl moiety, a carboxyl - substituted lower alkoxy group, carboxyl group, a lower alkoxycarbonyl- substituted lower alkoxy group, hydroxy group, a lower alkoxy-substituted lower alkoxy group, a lower alkenyloxy group, a lower alkanoyloxy-substituted lower alkyl group, a halogen-substituted lower alkyl group, a lower alkanoyl group, a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy-substituted lower alkoxy group, hydroxy group, a halogen atom and a lower alkoxy group on the phenyl moiety, a lower alkenyl group, a morpholinocarbonyl-lower alkoxy group, a lower alkylsufinyl group, an amino - substituted lower alkyl group having optionally a substituent selected from a lower alkylsulfonyl group and a lower alkanoyl group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkanoyloxy group, a 1 ,3-dioxolanyl - substituted lower alkyl group having optionally a lower alkyl substituent, a lower alkanoyl-substituted lower alkyl group, an aminocarbonyl-substituted lower alkyl group having optionally a lower alkyl substituent, a lower alkoxycarbonyl-substituted lower alkenyl group, an aminocarbonyl-substituted lower alkenyl group having optionally a lower alkyl substituent, a carboxyl - substituted lower alkenyl group, benzoyi group, a lower alkoxy-lower alkyl group, a group of the formula:
Figure imgf000475_0001
(in which s is an integer of 1 to 3, a group of the formula: A~~ is a 5- to 6 -
membered saturated or unsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R45 bonds to said heterocyclic group and is hydrogen atom, a lower alkyl group, a lower alkoxy-substituted lower alkyl group, phenyl group or oxo group), a group of the formula:
Figure imgf000475_0002
(in which t is an integer of 1 to 3, a group of the formula: A~~ is a lower alkyl group substituted by a 5- to 6-membered saturated or unsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R46 bonds to said heterocyclic group and is hydrogen atom, a lower alkyl group or oxo group), or a group of the formula: -(C=0)|NR9R10 (in which I is 0 or 1 , R9 and R10 are the same or different and each hydrogen atom, a lower alkanoyl group, a lower alkyl group, a morpholinocarbonyl-lower alkyl group, a cycloalkylcarbonyl group, a phenyl - lower alkenylcarbonyl group, a lower alkylsulfonyl group, an aminocarbonyl group having optionally a lower alkyl substituent, a phenylsulfonyl group having optionally a lower alkyl substituent on the phenyl moiety, a phenyl-lower alkenyl group, a benzoyi group having optionally 1 to 3 substituents selected from a halogen atom, a lower alkoxy group, an amino group having optionally a lower alkanoyl substituent and hydroxy group on the phenyl moiety, an amino - substituted lower alkanoyl group having optionally a lower alkanoyl substituent, an amino-substituted sulfonyl group having optionally a lower alkyl substituent, a phenyl-lower alkyl group, phenyl group, or an amino group having optionally a lower alkanoyl substituent, or R9 and R10 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom)); x) a group of the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); y) a 2,3-dihydro-1H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring; or z) a group of the formula:
Figure imgf000476_0001
(in which u is an integer of 1 to 3, a group of the formula: A~ is a lower alkenyl group substituted by a 5- to 14-membered saturated or unsaturated, heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R47 bonds on said heterocyclic group and is hydrogen atom, a halogen-substituted lower alkyl group, oxo group, a halogen atom, a lower alkoxy group, a lower alkyl group, a lower alkoxycarbonyl group, carboxyl group, an aminocarbonyl group having optionally a lower alkyl substituent, an amino group having optionally a lower alkanoyl substituent, a phenyl group having optionally a substituent selected from a lower alkoxy group and a halogen atom on the phenyl moiety, or a group of the formula:
Figure imgf000477_0001
(in which _A~~ , R45 and s are the same as defined above)),
or R3 and R4 may combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, provided that when R1 is hydrogen atom, R2 is methyl group, R3 is hydrogen atom, and m is 0, then R4 is not 2-(imidazol-2-yl)ethyl, 2-(indol-3 - yl)ethyl, or sec-butyl, or a salt thereof.
2. A quinoxaline derivative according to claim 1 , wherein m is 1 , or a salt thereof.
3. A quinoxaline derivative according to claim 1 , wherein m is 0, or a salt thereof.
4. A quinoxaline derivative according to claim 1 , wherein R1 is hydrogen atom, or a salt thereof.
5. A quinoxaline derivative according to claim 1 , wherein R1 is a halogen atom, a lower alkyl group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent, or a salt thereof.
6. A quinoxaline derivative according to claim 4, wherein R2 is a lower alkyl group having optionally a halogen substituent, or a salt thereof.
7. A quinoxaline derivative according to claim 4, wherein R2 is hydrogen atom, phenyl group, a morpholino-substituted lower alkyl group or an imidazolyl-substituted lower alkyl group, or a salt thereof.
8. A quinoxaline derivative according to claim 5, wherein R2 is a lower alkyl group having optionally a halogen substituent, or a salt thereof.
9. A quinoxaline derivative according to claim 5, wherein R2 is hydrogen atom, phenyl group, a morpholino-substituted lower alkyl group or an imidazolyl-substituted lower alkyl group, or a salt thereof.
10. A quinoxaline derivative according to claim 6, wherein R3 is hydrogen atom, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
Figure imgf000478_0001
(wherein the group A~ , R8 and q are as defined in claim 1), or a group of
the formula:
Figure imgf000478_0002
(wherein the group A λ , R47 and u are as defined in claim 1), or a salt
thereof.
11. A quinoxaline derivative according to claim 6, wherein R3 is hydrogen atom, a lower alkyl group, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
Figure imgf000479_0001
(in which A, R5 and p are as defined in claim 1); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; an alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); a 2,3 - dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2, 3-dihydro-1 H-indenyl ring, or a salt thereof.
12. A quinoxaline derivative according to claim 6, wherein R3 is a phenyl-lower alkoxycarbonyl group; a lower alkanoyl group; a lower alkoxy - lower alkyl group; a phenoxycarbonyl group; a lower alkanoyl-substituted lower alkyl group; a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring; a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); or a group of the formula:
Figure imgf000480_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above), and R4 is a group of the formula:
(R5)P
(in which A, R5 and p are as d --efine0d in claim 1); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (jn which A4 is a lower alkylene group, R40 and R4 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl - substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula:
Figure imgf000481_0001
(in which the group ( - R8 ancl are as defined in claim 1); a group of
the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 • dihydro-1 H-indenyl ring; or a group of the formula:
Figure imgf000481_0002
(in which the group __A~ , R47 and u are as defined in claim 1 ), or a salt
thereof.
13. A quinoxaline derivative according to claim 6, wherein R3 and R4 combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, or a salt thereof.
14. A quinoxaline derivative according to claim 7, wherein R3 is hydrogen atom, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
(R8)α
Figure imgf000481_0003
(wherein the group -Q- R8 and q are as defined in claim 1 ), or a group of the formula:
Figure imgf000482_0001
(wherein the group - _/T R47 and u are as defined in claim 1), or a salt
thereof.
15. A quinoxaline derivative according to claim 7, wherein R3 is hydrogen atom, a lower alkyl group, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
Figure imgf000482_0002
(in which A, R5 and p are as defined in claim 1); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; an alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); or a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, or a salt thereof.
16. A quinoxaline derivative according to claim 7, wherein R3 is a phenyl-lower alkoxycarbonyl group; a lower alkanoyl group; a lower alkoxy - lower alkyl group; a phenoxycarbonyl group; a lower alkanoyl-substituted lower alkyl group; a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring; a group of the formula: -E-N(R52)(R53)
(in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); or a group of the formula:
Figure imgf000483_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above), and R4 is a group of the formula:
Figure imgf000483_0002
(in which A, R5 and p are as defined in claim 1 ); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A -CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl - substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula:
Figure imgf000484_0001
(in which the group fT > R8 anc** °« are as defined in claim 1 ); a group of
the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 ■ dihydro-1 H-indenyl ring; or a group of the formula:
Figure imgf000484_0002
(in which the group ATA . R47 and u are as defined in claim 1 ), or a salt
thereof.
17. A quinoxaline derivative according to claim 7, wherein R3 and R4 combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, or a salt thereof.
18. A quinoxaline derivative according to claim 8, wherein R3 is hydrogen atom, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
Figure imgf000485_0001
(wherein the group A~ , R8 and q are as defined in claim 1), or a group of
the formula:
Figure imgf000485_0002
(wherein the group -©Λ■> 7 anc- u are as defined in claim 1), or a salt
thereof.
19. A quinoxaline derivative according to claim 8, wherein R3 is hydrogen atom, a lower alkyl group, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
Figure imgf000485_0003
(in which A, R5 and p are as defined in claim 1 ); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; an alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula: -As-CR^R^R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); or a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2, 3-dihydro-1 H-indenyl ring, or a salt thereof.
20. A quinoxaline derivative according to claim 8, wherein R3 is a phenyl-lower alkoxycarbonyl group; a lower alkanoyl group; a lower alkoxy - lower alkyl group; a phenoxycarbonyl group; a lower alkanoyl-substituted lower alkyl group; a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring; a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); or a group of the formula:
Figure imgf000487_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above), and R4 is a group of the formula:
Figure imgf000487_0002
(in which A, R5 and p are as defined in claim 1); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and
R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl - substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula:
Figure imgf000488_0001
(in which the group __/ . R8 and q are as defined in claim 1); a group of the
formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 - dihydro-1 H-indenyl ring; or a group of the formula:
(in which the group
Figure imgf000488_0002
thereof.
21. A quinoxaline derivative according to claim 8, wherein R3 and R4 combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, or a salt thereof.
22. A quinoxaline derivative according to claim 9, wherein R3 is hydrogen atom, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
Figure imgf000488_0003
(wherein the group -Q f^ - , R8 and q are as defined in claim 1), or a group of
the formula:
Figure imgf000489_0001
(wherein the group _ 7 \ , R47 a"d u are as defined in claim 1 ), or a salt
thereof.
23. A quinoxaline derivative according to claim 9, wherein R3 is hydrogen atom, a lower alkyl group, a lower alkanoyloxy-substituted lower alkyl group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyloxy-substituted lower alkyl group; and R4 is a group of the formula:
Figure imgf000489_0002
(in which A, R5 and p are as defined in claim 1 ); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; an alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); or a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring, or a salt thereof.
24. A quinoxaline derivative according to claim 9, wherein R3 is a phenyl-lower alkoxycarbonyl group; a lower alkanoyl group; a lower alkoxy - lower alkyl group; a phenoxycarbonyl group; a lower alkanoyl-substituted lower alkyl group; a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring; a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); or a group of the formula:
Figure imgf000490_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above), and R4 is a group of the formula:
Figure imgf000490_0002
(in which A, R5 and p are as defined in claim 1); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl - substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula:
Figure imgf000491_0001
(in which the group "~ , R8 and q are as defined in claim 1); a group of
the formula: -As-CR^R^R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3 dihydro-1 H-indenyl ring; or a group of the formula:
Figure imgf000491_0002
(in which the group __A~ , R47 and u are as defined in claim 1 ), or a salt
thereof.
25. A quinoxaline derivative according to claim 9, wherein R3 and R4 combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, or a salt thereof.
26. A quinoxaline derivative according to claim 10, wherein the saturated or unsaturated heterocyclic group in the lower alkyl group substituted by a 5- to 14-membered saturated or unsaturated heterocyclic groups represented by the group of /"~"N in the group of the formula:
Figure imgf000492_0001
is a member selected from the group consisting of benzofuryl, benzothienyl, indolyl, 2,3-dihydrobenzofuryl, perhydrobenzofuryl, quinolyl, benzimidazolyl, benzothiazolyl, imidazo[1 ,2-a]pyridyl, 1 ,4-benzodioxanyl, furo[3,2-c]pyridyl, 1 ,2,3,4-tetrahydrofuro[2,3-g]quinolyl, furo[2,3-g]quinolyl, 3,4-dihydrofuro[2,3 - gjquinolyl, thiazolyl, pyridyl, furyl, imidazolyl, 1 ,2,3,4-tetrazolyl, and oxazolyl, or a salt thereof.
27. A quinoxaline derivative according to claim 26, wherein the saturated or unsaturated heterocyclic group in the lower alkyl group substituted by a 5- to 14-membered saturated or unsaturated heterocyclic groups represented by the group of -0 /""*\ is benzofuryl or oxazolyl, or a salt
thereof.
28. A quinoxaline derivative according to claim 10, wherein the saturated or unsaturated heterocyclic group in the lower alkenyl group substituted by a 5- to 14-membered saturated or unsaturated heterocyclic groups represented by the group of in the 9rouP °f the formula:
Figure imgf000492_0002
Figure imgf000492_0003
is a member selected from the group consisting of benzofuryl, benzothienyl, carbostyril, 3,4-dihydrocarbostyril, benzothienyl, furo[3,2-c]pyridyl, furo[2,3-g] • quinolyl, 3,4-dihydrofuro[2,3-g]quinolyl, 1 ,2,3,4-tetrahydrofuro[2,3-g]quinolyl, naphtho[2,1-b]furyl, and oxazolyl, or a salt thereof.
29. A quinoxaline derivative according to claim 28, wherein the saturated or unsaturated heterocyclic group in the lower alkenyl group substituted by a 5- to 14-membered saturated or unsaturated heterocyclic groups represented by the group of is benzofuryl, or a salt thereof.
Figure imgf000493_0001
30. A quinoxaline derivative according to claim 1 , which is a member selected from the group consisting of 2-[3-(benzofuran-2-yl)-2 - butenylaminocarbonyl]-3-methylquinoxalin-4-oxide, 2-[(3-methyl-7-trifluoro - methylbenzofuran-2-yl)methylaminocarbonyl]-3-methylquinoxalin-4-oxide, 2 - [(2-phenyl-5-methyloxazol-4-yl)methylaminocarbonyl]-3-methylquinoxalin-4 - oxide, 2-{[5-(2,5-dimethylthiazol-4-yl)benzofuran-3-yl]methylaminocarbonyl}-3 - methylquinoxalin-4-oxide, 2-{3-[5-(2-methyl-1 ,2,3,4-tetrazol-5-yl)benzofuran-2 - yl]-2-butenylaminocarbonyl}-3-methylquinoxalin-4-oxide, 2-[5-(benzofuran-2 - yl)-2,4-hexadienylaminocarbonyl]-3-methylquinoxalin-4-oxide, 2-{3-[5-(2,5 - dimethylthiazol-4-yl)benzofuran-2-yl]-2-butenylaminocarbonyl}-3-methyl - quinoxalin-4-oxide, 2-{3-[5-(thiazol-2-yl)benzofuran-2-yl]-2-butenylamino - carbonyl}-3-methylquinoxalin-4-oxide, 2-[3-(5,7-difiuorobenzofuran-2-yl)-2 - butenylaminocarbonyl]-3-methylquinoxalin-4-oxide, 2-{N-[3-(benzofuran-2-yl) -
2-butenyl]-N-methoxycarbonylaminocarbonyl}-3-methylquinoxalin-4-oxide, 2 - {N-[3-(benzofuran-2-yl)-2-butenyl]-N-propanoyloxymethylaminocarbonyl}-3 - methylquinoxalin-4-oxide, 2-{N-[3-(benzofuran-3-yl)-2-butenyl]-N-acetyloxy - methylaminocarbonyl}-3-methylquinoxalin-4-oxide, 2-{N-[3-(benzofuran-2-yl)-2 • butenyl]-N-ethoxycarbonyloxymethylaminocarbonyl}-3-methylquinoxalin-4 - oxide, 2-{N-[3-methyl-7-trifluoromethylbenzofuran-2-yl)methyl]-N-acetoxy - methylaminocarbonyl}-3-methylquinoxalin-4-oxide, and 2-{N-[2-phenyl-5 - methyloxazol-4-yl)methyl]-N-acetoxymethylaminocarbonyl}-3-methylquinoxalin ■ 4-oxide, or a salt thereof.
31. An antidiabetic agent which comprises as an active ingredient a compound as set forth in claim 1.
32. An antidiabetic agent which comprises as an active ingredient a quinoxaline derivative of the formula:
Figure imgf000494_0001
wherein R1 is hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, or an aminocarbonyl group having optionally a lower alkyl substituent,
R2 is hydrogen atom, a lower alkyl group having optionally a halogen substituent, phenyl group, a morpholino-substituted lower alkyl group or an imidazolyl-substituted lower alkyl group, n and m are each 0 or 1 , r is 1 or 2,
R3 and R4 are the same or different and each a) hydrogen atom; b) a lower alkyl group; c) a phenyl-lower alkoxycarbonyl group; d) a lower alkanoyloxy-substituted lower alkyl group; e) a lower alkanoyl group; f) a lower alkoxycarbonyl group; g) a lower alkoxy-lower alkyl group; h) a phenoxy - carbonyl group; i) a lower alkanoyl-substituted lower alkyl group; j) a lower alkoxycarbonyloxy-substituted lower alkyl group; k) a benzoyl-substituted lower alkyl group having optionally a halogen substituent on the phenyl ring; I) a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); m) a group of the formula:
Figure imgf000495_0001
(in which R54 is hydrogen atom or a lower alkyl group and A is the same as defined above); n) a group of the formula:
Figure imgf000495_0002
(in which A is the same as defined above, p is an integer of 1 to 3, R5 is hydrogen atom, a lower alkoxy-substituted lower alkoxy group, a lower alkoxy group, an amino group having optionally a lower alkyl substituent, a halogen atom, nitro group, hydroxy group, a lower alkyl group having optionally a hydroxy substituent, a lower alkenyloxy group, a carboxyl-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a lower alkoxycarbonyl group, a halogen-substituted lower alkoxy group, a hydroxy - substituted lower alkoxy group, a phenyl-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkoxy group on the phenyl moiety, a 1 ,3-dioxolanyl group having optionally a lower alkyl substituent, a lower alkanoyl group, a morpholino-substituted lower alkoxy group, a morpholino-substituted lower alkyl group, a morpholinocarbonyl group or a group of the formula: -Y-A*)-CONR6R7 (in which A-\ is a lower alkylene group, Y is a group of the formula: -O- or a group of the formula: -NH-, R6 and R7 are the same or different and each hydrogen atom, a lower alkyl group having optionally a hydroxy substituent, a phenyl-lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, a furyl-substituted lower alkyl group, or a lower alkoxy-substituted lower alkyl group, or R6 and R7 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with nitrogen atom or oxygen atom, said heterocyclic group having optionally 1 to 3 substituents selected from hydroxy group, a lower alkyl group and a phenyl-lower alkyl group)); o) a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy-substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4 is a lower alkylene group, R40 and R41 are the same or different and each hydrogen atom or a lower alkyl group, or R40 and R41 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; p) an alkenyl group; q) a cycloalkyl-lower alkyl group; r) a naphthyl-lower alkyl group; s) a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; t) a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; u) a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; v) a phenoxy-substituted lower alkyl group; w) a group of the formula:
Figure imgf000496_0001
(in which q is an integer of 1 to 3, a group of the formula: f is a lower
alkyl group substituted by a 5- to 14-membered saturated or unsaturated heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R8 substitutes on the above heterocyclic group, and is hydrogen atom, oxo group, a lower alkyl group having optionally a hydroxy substituent, a halogen atom, nitro group, a lower alkoxy group, cyano group, a lower alkoxycarbonyl group, a phenyl-lower alkoxy group having optionally an amino group having optionally a lower alkanoyl substituent on the phenyl moiety, a carboxyl - substituted lower alkoxy group, carboxyl group, a lower alkoxycarbonyl - substituted lower alkoxy group, hydroxy group, a lower alkoxy-substituted lower alkoxy group, a lower alkenyloxy group, a lower alkanoyloxy-substituted lower alkyl group, a halogen-substituted lower alkyl group, a lower alkanoyl group, a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy-substituted lower alkoxy group, hydroxy group, a halogen atom and a lower alkoxy group on the phenyl moiety, a lower alkenyl group, a morpholinocarbonyl-lower alkoxy group, a lower alkylsufinyl group, an amino - substituted lower alkyl group having optionally a substituent selected from a lower alkylsulfonyl group and a lower alkanoyl group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkanoyloxy group, a 1 ,3-dioxolanyl - substituted lower alkyl group having optionally a lower alkyl substituent, a lower alkanoyl-substituted lower alkyl group, an aminocarbonyl-substituted lower alkyl group having optionally a lower alkyl substituent, a lower alkoxy - carbonyl-substituted lower alkenyl group, an aminocarbonyl-substituted lower alkenyl group having optionally a lower alkyl substituent, a carboxyl-substituted lower alkenyl group, benzoyi group, a lower alkoxy-lower alkyl group, a group of the formula:
Figure imgf000497_0001
(in which s is an integer of 1 to 3, a group of the formula: A~\ is a 5- to 6 -
membered saturated or unsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R45 bonds to said heterocyclic group and is hydrogen atom, a lower alkyl group, a lower alkoxy-substituted lower alkyl group, phenyl group or oxo group), a group of the formula:
(R46)t
Figure imgf000497_0002
(in which t is an integer of 1 to 3, a group of the formula: A~ is a lower alkyl group substituted by a 5- to 6-membered saturated or unsaturated heterocyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R46 bonds to said heterocyclic group and is hydrogen atom, a lower alkyl group or oxo group), or a group of the formula: -(C=0)|NR9R1o (in which I is 0 or 1 , R9 and R1° are the same or different and each hydrogen atom, a lower alkanoyl group, a lower alkyl group, a morpholinocarbonyl-lower alkyl group, a cycloalkylcarbonyl group, a phenyl - lower alkenylcarbonyl group, a lower alkylsulfonyl group, an aminocarbonyl group having optionally a lower alkyl substituent, a phenylsulfonyl group having optionally a lower alkyl substituent on the phenyl moiety, a phenyl-lower alkenyl group, a benzoyi group having optionally 1 to 3 substituents selected from a halogen atom, a lower alkoxy group, an amino group having optionally a lower alkanoyl substituent and hydroxy group on the phenyl moiety, an amino - substituted lower alkanoyl group having optionally a lower alkanoyl substituent, an amino-substituted sulfonyl group having optionally a lower alkyl substituent, a phenyl-lower alkyl group, phenyl group, or an amino group having optionally a lower alkanoyl substituent, or R9 and R10 may combine together with the adjacent nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom)); x) a group of the formula: -A5-CR42R43R44 (in which A5 is a lower alkylene group, R42 and R43 combine together to form a group of the formula: =0, or =N-OH or a lower alkylenedioxy group, and R44 is a phenyl group having optionally a lower alkoxy substituent on the phenyl moiety); y) a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring; or z) a group of the formula:
Figure imgf000498_0001
(in which u is an integer of 1 to 3, a group of the formula: _A~ is a lower
alkenyl group substituted by a 5- to 14-membered saturated or unsaturated, heteromonocyclic, heterobicyclic or heterotricyclic group having 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, R47 bonds on said heterocyclic group and is hydrogen atom, a halogen-substituted lower alkyl group, oxo group, a halogen atom, a lower alkoxy group, a lower alkyl group, a lower alkoxycarbonyl group, carboxyl group, an aminocarbonyl group having optionally a lower alkyl substituent, an amino group having optionally a lower alkanoyl substituent, a phenyl group having optionally a substituent selected from a lower alkoxy group and a halogen atom on the phenyl moiety, or a group of the formula:
Figure imgf000499_0001
(in which agroup of the formula: A~~ , R45 and s are the same as defined
above)), or R3 and R4 may combine together with the adjacent nitrogen atom to which they bond to form 1 ,2,3,4-tetrahydroisoquinolyl group, said heterocyclic group having optionally a lower alkoxy substituent, or a pharmaceutically acceptable salt thereof.
33. A process for preparing a quinoxaline derivative as set forth in claim 1 , which comprises
(a) reacting a quinoxaline compound of the formula:
Figure imgf000499_0002
(2) (wherein R1 , R2, m, n, and r are as defined in claim 1 ) or a reactive derivative thereof with an amine of the formula: HNR3R4 (wherein R3 and R4 are as defined in claim 1),
(b) reacting a quinoxaline compound of the formula:
Figure imgf000500_0001
(0)„
(1a)
(wherein R3a is hydrogen atom; a lower alkyl group; a phenyl-lower alkoxycarbonyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkanoyl group; a lower alkoxycarbonyl group; a lower alkoxy-lower alkyl group; a phenoxycarbonyl group; a lower alkanoyl-substituted lower alkyl group; a lower alkoxycarbonyloxy-substituted lower alkyl group; a benzoyi - substituted lower alkyl group, having optionally a halogen substituent on the phenyl ring; a group of the formula: -E-N(R52)(R53) (in which R52 and R53 are the same or different and each hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group or phenyl group, or R52 and R53 may combine together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or oxygen atom, E is a lower alkylene group, a group of the formula: -CO-, or a group of the formula: -CO-A- (in which A is a lower alkylene group)); a group of the formula:
Figure imgf000500_0002
(in which R54 is hydrogen atom o a lower alkyl group and A is the same as defined above); a group of the formula:
(R5)c
(wherein A, R5 and p are as defin -edø in claim 1); a phenyl-lower alkenyl group having optionally a substituent selected from a lower alkoxy group, a halogen atom, an amino group having optionally a substituent selected from a lower alkanoyl group and a phenyl-lower alkenylcarbonyl group, a lower alkoxy - substituted lower alkoxy group, a tetrazolyl group having optionally a lower alkyl substituent on the tetrazole moiety, hydroxy group, a group of the formula: -O-A4-CO-NR40R41 (in which A4, R40 and R41 are as defined in claim 1), a lower alkenyloxy group, nitro group and a lower alkyl group having optionally a halogen substituent on the phenyl moiety; an alkenyl group; a cycloalkyl-lower alkyl group; a naphthyl-lower alkyl group; a phenylthio-substituted lower alkyl group having optionally a lower alkoxy-substituent on the phenyl moiety; a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety; a phenoxy - substituted lower alkyl group; a group of the formula:
Figure imgf000501_0001
(in which A~ , R8 and q are as defined in claim 1); a group of the formula:
-A5-CR R43R44 (in which A5, R42, R43, and R44 are as defined in claim 1 ); a 2,3-dihydro-1 H-indenyl-substituted lower alkyl group having optionally a substituent selected from oxo group, hydroxy group and a silyloxy group having a lower alkyl substituent on the 2,3-dihydro-1 H-indenyl ring; or a group of the formula:
Figure imgf000501_0002
(in which -Q , R47 and u are as defined in claim 1), and R1, R2, m, n, and r
are as defined in claim 1 ) with a compound of the formula: R3bX or R3cCOR3d (wherein R3b is the same as R3a other than hydrogen atom, and R3c and R3d are each hydrogen atom or a lower alkyl group), to give a quinoxaline compound of the formula:
Figure imgf000502_0001
(0)n
(1 b)
(wherein R1, R2, m, n, and r are as defined in claim 1 , and R3a and R3b are as defined above), c) oxidizing a quinoxaline compound of the formula:
Figure imgf000502_0002
(1C)
(wherein R1, R2, R3, R4, n, and r are as defined in claim 1) with an oxidizing agent to convert into a compound of the formula:
Figure imgf000502_0003
(1d) (wherein R1, R2, R3, R4, n, and r are as defined in claim 1 ), d) oxidizing a quinoxaline compound of the formula:
Figure imgf000503_0001
(1 N)
(wherein R26 is a phenylthio-substituted lower alkoxy group having optionally a lower alkoxy substituent on the phenyl moiety, R1, R2, m, n, and r are as defined in claim 1 , and R3a is as defined above) with an oxidizing agent to convert into a compound of the formula:
Figure imgf000503_0002
(10)
(wherein R27 is a phenylsulfinyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, R1, R2, m, n, and r are as defined in claim 1 , and R3a is as defined above), and further to convert into a compound of the formula:
Figure imgf000503_0003
(1 P) (wherein R28 is a phenylsulfonyl-substituted lower alkyl group having optionally a lower alkoxy substituent on the phenyl moiety, R1, R2, m, n, and r are as defined in claim 1 , and R3a is as defined above), e) oxidizing a quinoxaline compound of the formula:
Figure imgf000504_0001
(0)n
(1 N)
(wherein R1 , R2, m, n, and r are as defined in claim 1 , and R3a and R26 are as defined above) with an oxidizing agent to convert into a compound of the formula:
Figure imgf000504_0002
(1 P)
(wherein R1, R2, m, n, and r are as defined in claim 1 , and R3a and R28 are as defined above), or f) reacting a quinoxaline compound of the formula:
Figure imgf000505_0001
(1a)
(wherein R1, R2, m, n, and r are as defined in claim 1 , and R3a is as defined above) with a compound of the formula: R3cOH (in which R3c is as defined above) to give a compound of the formula:
Figure imgf000505_0002
(1 Y) (wherein R1, R2, m, n, and r are as defined in claim 1 , and R3a is as defined above, and R3c' is a phenyl-lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a phenoxycarbonyl group, or a group of the formula: -CO-A-NR52R53 (in which A, R52, R53 are the same as defined above).
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WO1998055454A2 (en) * 1997-06-05 1998-12-10 Takeda Chemical Industries, Ltd. Benzofurans and benzothophenes as suppressors of neurodegeneration
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US8642620B2 (en) 2005-06-28 2014-02-04 Sanofi Heteroaryl-substituted amides comprising an unsaturated or cyclic linker group, and their use as pharmaceuticals
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KR100196356B1 (en) 1999-06-15
CN1114834A (en) 1996-01-10
TW284760B (en) 1996-09-01
KR950704269A (en) 1995-11-17

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