CA2455453A1 - Taxol enhancer compounds - Google Patents

Taxol enhancer compounds Download PDF

Info

Publication number
CA2455453A1
CA2455453A1 CA002455453A CA2455453A CA2455453A1 CA 2455453 A1 CA2455453 A1 CA 2455453A1 CA 002455453 A CA002455453 A CA 002455453A CA 2455453 A CA2455453 A CA 2455453A CA 2455453 A1 CA2455453 A1 CA 2455453A1
Authority
CA
Canada
Prior art keywords
substituted
group
methyl
nhr
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002455453A
Other languages
French (fr)
Other versions
CA2455453C (en
Inventor
Keizo Koya
Lijun Sun
Shoujun Chen
Noriaki Tatsuta
Yaming Wu
Mitsunori Ono
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Synta Phamaceuticals Corp
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2455453A1 publication Critical patent/CA2455453A1/en
Application granted granted Critical
Publication of CA2455453C publication Critical patent/CA2455453C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A45—HAND OR TRAVELLING ARTICLES
    • A45D—HAIRDRESSING OR SHAVING EQUIPMENT; EQUIPMENT FOR COSMETICS OR COSMETIC TREATMENTS, e.g. FOR MANICURING OR PEDICURING
    • A45D8/00—Hair-holding devices; Accessories therefor
    • A45D8/004—Hair-holding devices; Accessories therefor with decorative arrangements or form
    • A45D8/006—Interchangeable ornaments attached to hair holding devices
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/275—Nitriles; Isonitriles
    • A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/38—Amides of thiocarboxylic acids
    • C07C327/56—Amides of thiocarboxylic acids having nitrogen atoms of thiocarboxamide groups further bound to another hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
    • C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
    • C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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 ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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
    • C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Abstract

Disclosed is a compound represented by the Structural Formula (I); Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or -C(R7R8)-. R1 and R2 are independently an aryl group or a substituted aryl group, R3 and R4 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R5-R6 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R7 and R8 are each independently -H, an aliphatic or substituted aliphatic group, or R7 is -H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstitut ed alkylene group. Z is =O or =S. Also disclosed are pharmaceutical composition s comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with taxol or an analog of taxol.

Claims (117)

1. A compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein:
Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z
groups to which it is bonded, is a substituted or unsubstituted aromatic group;
R1 and R2 are independently an aryl group or a substituted aryl group;
R3 and R4 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;
R5-R6 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group; and Z is =O or =S;
provided that when Y is -CH2-, R3 and R4 are both phenyl and R5-R6 are all -H, then R1 and R2 are not both phenyl.
2. The compound of Claim 1 wherein Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group;
3. The compound of Claim 2 wherein Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted arylene group.
4. The compound of Claim 3 wherein the compound is represented by the following structural formula:

wherein Ring A is substituted or unsubstituted and W is -CH- or -N-.
5. The compound of Claim 2 wherein Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group.
6. The compound of Claim 2 wherein the compound is represented by the following structural formula:

wherein Y' is a covalent bond or -CR7R8- and R7 and R8 are each independently -H, an aliphatic or substituted aliphatic group, or R7 is -H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group.
7. The compound of Claim 6 wherein at least one of R1-R4 is a heteroaryl group, a substituted heteroaryl group, or a phenyl group substituted with at least one group other than an aliphatic group when R5-R8 are all -H.
8. The compound of Claim 6 wherein at least one of R1-R4 is a heteroaryl group, a substituted heteroaryl group, or a phenyl group substituted with at least one group other than an aliphatic group.
9. The compound of Claim 8 wherein R3 and R4 are both methyl.
10. The compound of Claim 6 wherein the compound is represented by the following structural formula:

wherein Y" is a covalent bond or -CH2-.
11. The compound of Claim 10 wherein R1 and R2 are different and/or R3 and R4 are different.
12. The compound of Claim 10 wherein R1 and R2 are the same and R3 and R4 are the same.
13. The compound of Claim 12 Wherein R3 and R4 are both a lower alkyl group or a substituted lower alkyl group.
14. The compound of Claim 13 wherein R3 and R4 are both a lower alkyl group substituted with substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR8 a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d -C(=NH)-NHR a, -NR d -C(=NH)-N(R a R b), -NR d -C(=NR c)-NH2, -NR d -C(=NR c)-NHR a, -NR d -C(=NR c)-N(R a R b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c=CR a R b,-CR c =CHR a, -CR c =CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a -R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d, taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
15. The compound of Claim 13 wherein R3 and R4 are both methyl or ethyl.
16. The compound of Claim 15 wherein R1 and R2 are both a phenyl group substituted with at least one group other than an aliphatic group; or R1 and R2 are both heteroaryl or substituted heteroaryl groups.
17. The compound of Claim 12 wherein R3 and R4 are both a heteroaryl group or a substituted heteroaryl group.
18. The compound of Claim 17 wherein R1 and R2 are both a substituted or unsubstituted phenyl group; or R1 and R2 are both a substituted or unsubstituted heteroaryl group.
19. The compound of Claim 12 wherein R3 and R4 are both a substituted phenyl group.
20. The compound of Claim 19 wherein R3 and R4 are both a phenyl group substituted with at least one group other than an aliphatic group.
21. The compound of Claim 20 wherein R1 and R2 are both heteroaryl or substituted heteroaryl groups; or R1 and R2 are both substituted or unsubstituted phenyl groups.
22. The compound of Claim 19 wherein R3 and R4 are both a phenyl group substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR
a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH a, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d -C(=NH)-NHR a, -NR d -C(=NH)-N(R a R b), -NR d -C(=NR c)-NH2, -NR a -C(=NR c)-NHR a, -NR a -C(=NR c)-N(R a R b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c =CR a R b, -CR c =CHR a, -CR c =CR a R b, -CCR a, -SH, -SR
a, -S(O)R a, -S(O)2R a, alkyl group, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a -R a are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d , taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group
23. The compound of Claim 12 wherein R1 and R2 are both a heteroaryl group or a substituted heteroaryl group.
24. The compound of Claim 12 wherein R1 and R2 are both a substituted phenyl group.
25. The compound of Claim 12 wherein R1 and R2 are both a phenyl group substituted with at least one group other than an aliphatic group.
26. The compound of Claim 24 wherein R1 and R2 are both a phenyl group substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR
a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR a H-C(=NH)-NH2, -NR d -C(=NH)-NHR a, -NR d -C(=NH)-N(R a R b), -NR d -C(=NR c)-NH2, -NR d -C(=NR c)-NHR a, -NR a-C(=NR c)-N(R a R b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c =CR a R b,-CR c =CHR a, -CR c =CR a R b, -CCR a, -SH, -SR
a, -S(O)R a, -S(O)2R a, alkyl group, susbstituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a -R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d, taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
27. The compound of Claim 5 wherein the compound is represented by the following structural formula:

wherein Y' is a covalent bond or -CR7R8-.
28. The compound of Claim 27 wherein R7 and R8 are different.
29. The compound of Claim 27 where R1 and R2 are the same; and R3 and R4 are the same.
30. The compound of Claim 27 wherein R1 and R2 are both aryl or substituted aryl groups and R3 and R4 are both a lower alkyl group or a substituted lower alkyl group.
31. The compound of Claim 30 wherein R1 and R2 are both phenyl or substituted phenyl and R3 and R4 are both methyl, ethyl, phenyl, or thienyl.
32. The compound of Claim 31 wherein R7 and R8 are both methyl or wherein R7 and R8, taken together, are propylene or butylene.
33. The compound of Claim 31 wherein R7 is -H and R8 is lower alkyl, thienyl, phenyl or benzyl.
34. The compound of Claim 31 wherein R1 and R2 are both phenyl substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR a, -O-COR a, -COR
a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d -C(=NH)-NHR a, -NR d -C(=NH)-N(R a R b), -NR d -C(=NR c)-NH2, -NR d -C(=NR c)-NHR a, -NR d -C(=NR c)-N(R a R b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c =CR a R b,-CR c =CHR a, -CR c =CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl group, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a -R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d, taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
35. A compound represented by the following structural formula:

or a physiologically acceptable salt thereof, wherein:
Y' is a covalent bond or -CR7R8-;
R1 and R2 are both a substituted or unsubstituted aryl group;
R3 and R4 are both -H, methyl or ethyl; and R7 is -H and R8 is -H or methyl.
36. The compound of Claim 34 wherein R1 and R2 are both phenyl substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR a, -O-COR a, -COR
a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH a, CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d -C(=NH)-NHR a, -NR d -C(=NH)-N(R a R b), -NR d -C(=NR c)-NH2, -NR d -C(=NR c)-NHR a, -NR d -C(=NR c)-N(R a R b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c =CR a R b,-CR c =CHR a, -CR c =CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl group, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a -R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d, taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
37. The compound of Claim 6 wherein R5 and R6 are the same.
38. The compound of Claim 37 wherein the compound is represented by the following structural formula:

wherein Y" is a covalent bond or -CH2.
39. The compound of Claim 38 wherein R5 and R6 are both a lower alkyl group or a phenyl group.
40. The compound of Claim 39 wherein R5 and R6 are both a methyl group.
41. The compound of Claim 39 wherein R1 and R2 are both phenyl or substituted phenyl; R3 and R4 are both a lower alkyl group; and R5 and R6 are both a lower alkyl group.
42. A compound represented by the following structural formula:

or a physiologically acceptable salt thereof, wherein a) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H;

b) R1 and R2 are both phenyl; R3 and R4 are both ethyl; R7 and R8 are both -H;
c) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
d) R1 and R2 are both 4-methoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
e) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
R1 and R2 are both phenyl; R3 and R4 are both ethyl; R7 is methyl; R8 is -H;
g) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
h) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
i) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
j) R1 and R2 are both 3-cyanophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
k) R1 and R2 are both 3-fluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
l) R1 and R2 are both 4-chlorophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
m) R1 and R2 are both 2-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
n) R1 and R2 are both 3-methoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
o) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
p) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
q) R1 and R2 are both 2,5-difluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;

r) R1 and R2 are both 2,5-difluorophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
s) R1 and R2 are both 2,5-dichlorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
t) R1 and R2 are both 2,5-dimethylphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
u) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
v) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H; and w) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H.
43. A compound represented by the following structural formula:
or a physiologically acceptable salt thereof, wherein:
a) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
b) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
c) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
d) R1 and R2 are both 3-fluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H; and e) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H.
f) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H
44. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
Y is a covalent bond, phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z
groups to which it is bonded, is a substituted or unsubstituted aromatic group;
R1 and R2 are independently an aryl group or a substituted aryl group, R3 and R4 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;
R5-R6 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group; and Z is =O or =S.
45. The pharmaceutical composition of Claim 44 wherein Y is a covalent bond, phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group;
46. The pharmaceutical composition of Claim 45 wherein Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group.
47. The pharmaceutical composition of Claim 46 wherein the compound is represented by the following structural formula:

wherein Ring A is substituted or unsubstituted and W is -CH- or -N-.
48. The pharmaceutical composition of Claim 45 wherein Y is a covalent bond or a substituted or unsubstituted hydrocarbyl group.
49. The pharmaceutical composition of Claim 45 wherein the compound is represented by the following structural formula:
wherein Y' is a covalent bond or -CR7R8- and R7 and R8 are each independently -H, an aliphatic or substituted aliphatic group, or R7 is -H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group.
50. The pharmaceutical composition of Claim 45 wherein the compound is represented by the following structural formula:
wherein Y" is a covalent bond or -CH2-.
51. The pharmaceutical composition of Claim 50 wherein R1 and R2 are different and/or R3 and R4 are different.
52. The pharmaceutical composition of Claim 50 wherein R1 and R2 are the same and R3 and R4 are the same.
53. The pharmaceutical composition of Claim 52 wherein R3 and R4 are both a lower alkyl group or a substituted lower alkyl group.
54. The pharmaceutical composition of Claim 53 wherein R3 and R4 are both methyl or ethyl.
55, The pharmaceutical composition of Claim 54 wherein R1 and R2 are both an aryl or substituted aryl group.
56. The pharmaceutical composition of Claim 54 wherein R1 and R2 are both a phenyl group or a substituted phenyl group.
57. The pharmaceutical composition of Claim 54 wherein R1 and R2 are both a phenyl group substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R
b), -COOR a, -CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d-C(=NH)-NHR a, -NR d-C(=NH)-N(R a R b), -NR d-C(=NR c)-NH2, -NR d-C(=NR c)-NHR a, -NR d-C(=NR c)-N(R a R
b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c=CR a R b,-CR c=CHR a, -CR a=CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl group, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a-R d are independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d, taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
58. The pharmaceutical composition of Claim 52 wherein R3 and R4 are both a phenyl group or a substituted phenyl group.
59 59. The pharmaceutical composition of Claim 58 wherein R1 and R2 are both a phenyl or substituted phenyl group.
60. The pharmaceutical composition of Claim 52 wherein R1 and R2 are both a substituted phenyl group.
61. The pharmaceutical composition of Claim 49 wherein the compound is represented by the following structural formula:
wherein Y' is a covalent bond or -CR7R8-.
62. The pharmaceutical composition of Claim 61 wherein R7 and R8 are different.
63. The pharmaceutical composition of Claim 61 where R1 and R2 are the same;

and R4 are the same; and R7 and R8 are the same.
64. The pharmaceutical composition of Claim 61 wherein R1 and R2 are both aryl or substituted aryl groups and R3 and R4 are both a lower alkyl group or a substituted lower alkyl group.
65. The pharmaceutical composition of Claim 61 wherein R1 and R2 are both phenyl or substituted phenyl and R3 and R4 are methyl, ethyl, phenyl, or thienyl.
66. The pharmaceutical composition of Claim 65 wherein R7 and R8 are both methyl or wherein R7 and R8, taken together, are propylene or butylene.
67. The pharmaceutical composition of Claim 65 wherein R7 is -H and R8 is lower alkyl, thienyl, phenyl or benzyl.
68. The pharmaceutical composition of Claim 65 wherein R1 and R2 are both phenyl substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR
a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a,-CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2,-NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b),-C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, NH-C(=NC c)-NHR a,-NH-N(R a R b), -NR d H-C(=NH)-NH2, -NR d-C(=NH)-NHR a, -NR d-C(=NH)-N(R a R b),-NR d-C(=NR c)-NH2, -NR d-C(=NR c)-NHR a, -NR d-C(=NR c)-N(R a R b),-NHNH2,-NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a,-CH=CR a R b, -CR c=CR a R b,-CR c=CHR a, -CR c=CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl groups, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a-R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or.
substituted aromatic group, or,-NR a R d, taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
69. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula:
or a physiologically acceptable salt thereof, wherein:
Y' is a covalent bond or -CR7R8-;
R1 and R2 are both a substituted or unsubstituted aryl group;
R3 and R4 are both -H, methyl or ethyl; and R7 is -H and R8 is -H or methyl.
70. The pharmaceutical composition of Claim 69 wherein R1 and R2 are both phenyl substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR
a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a,-CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH a,-NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b),-C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR o)-NH2,-NH-C(=NR c)-NHR a,-NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d-C(=NH)-NHR a, -NR d-C(=NH)-N(R a R b),-NR d-C(=NR c)-NH2, -NR d-C(=NR c)-NHR a, -NR d-C(=NR c)-N(R a R b),-NHNH2, NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a,-CH=CR a R b, -CR c=CR a R b,-CR c=CHR a, -CR c=CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl groups, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a-R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d, taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
71. The pharmaceutical composition of Claim 49 wherein R5 and R6 are the same.
72. The pharmaceutical composition of Claim 71 wherein the compound is represented by the following structural formula:
wherein Y" is a covalent bond or -CH2-.
73. The pharmaceutical composition of Claim 72 wherein R5 and R6 are both a lower alkyl group or a phenyl group.
74. The pharmaceutical composition of Claim 73 wherein R5 and R6 are both a methyl group.
75. The pharmaceutical composition of Claim 72 wherein R1 and R2 are both phenyl or substituted phenyl; R3 and R4 are both a lower alkyl group; and R5 and R6 are both a lower alkyl group.
76. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula:

or physiologically acceptable salt thereof, wherein:
a) R and R2 are both phenyl; R3 and R4 are both phenyl; R7 and R8 are both -H;
b) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
c) R1 and R2 are both phenyl; R3 and R4 are both ethyl; R7 and R8 are both -H;
d) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
e) R1 and R2 are both 4-methoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
f) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 is methyl;R8 is H;
g) R1 and R2 are both phenyl; R3 and R4 are both ethyl; R7 is methyl; R8 is -H;
h) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
i) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
j) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
k) R1 and R2 are both 3-cyanophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
l) R1 and R2 are both 3-fluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
m) R1 and R2 are both 4-chlorophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
n) R1 and R2 are both 2-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
o) R1 and R2 are both 3-methoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;

p) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
q) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
r) R1 and R2 are both 2,5-difluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
s) R7 and R2 are both 2,5-difluorophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
t) R1 and R2 are both 2,5-dichlorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
u) R1 and R2 are both 2,5-dimethylphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
v) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
w) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H; and x) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H.
77. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula:
or a physiologically acceptable salt thereof, wherein:
a) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
b) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
c) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
d) R1 and R2 are both 3-fluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;

e) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
f) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H; and g) R1 and R2 are both phenyl; R3 and R4 are both phenyl; R7 and R8 are both -H.
78. A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of taxol or a taxol analog and an effective amount of a compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
Y is a covalent bond, phenylene group or a substituted or unsubstituted hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group;
R1 and R2 are independently an aryl group or a substituted aryl group;
R3 and R4 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;
R5-R6 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;
and Z is =O or =S.
79. The method of Claim 78 wherein Y is a covalent bond, phenylene group or a substituted or unsubstituted hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group.
80. The method of Claim 79 wherein Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group.
81. The method of Claim 80 wherein the compound is represented by the following structural formula:
wherein Ring A is substituted or unsubstituted and W is -CH- or -N-.
82. The method of Claim 79 wherein Y is a covalent bond or a substituted or unsubstituted straight chained hydrcarbyl group.
83. The method of Claim 79 wherein the compound is represented by the following structural formula:
wherein Y' is a covalent bond or -CR7R8- and R7 and R8 are each independently -H, an aliphatic or substituted aliphatic group, or R7 is -H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group.
84. The method of Claim 83 wherein the taxol analog is represented by a structural formula selected from:

wherein:
R10 is a lower alkyl group, a substituted lower alkyl group, a phenyl group, a substituted phenyl group, -SR19, -NHR19 or -OR19;
R11 is a lower alkyl group, a substituted lower alkyl group, an aryl group or a substituted aryl group;
R12 is -H, -OH, lower alkyl, substituted lower alkyl, lower alkoxy, substituted lower alkoxy, -O-C(O)-(lower alkyl), -O-C(O)-(substituted lower alkyl), -O-CH2-O-(lower alkyl) -S-CH2-O-(lower alkyl);
R13 is -H, -CH3, or, taken together with R14, -CH2-;
R14 is -H, -OH, lower alkoxy, -O-C(O)-(lower alkyl), substituted lower alkoxy, -O-C(O)-(substituted lower alkyl), -O-CH2-O-P(O)(OH)2, -O-CH2-O-(lower alkyl), -O-CH2-S-(lower alkyl) or, taken together with R20, a double bond;

R15 -H, lower acyl, lower alkyl, substituted lower alkyl, alkoxymethyl, alkthiomethyl, -OC(O)-O(lower alkyl), -OC(O)-O(substituted lower alkyl), -OC(O)-NH(lower alkyl) or -OC(O)-NH(substituted lower alkyl);
R16 is phenyl or substituted phenyl;
R17 is -H, lower acyl, substituted lower acyl, lower alkyl, substituted, lower alkyl, (lower alkoxy)methyl or (lower alkyl)thiomethyl;
R18 -H, -CH3 or, taken together with R17 and the carbon atoms to which R17 and R18 are bonded, a five or six membered a non-aromatic heterocyclic ring;
R19 is a lower alkyl group, a substituted lower alkyl group, a phenyl group, a substituted phenyl group;
R20 is -H or a halogen; and R21 is -H, lower alkyl, substituted lower alkyl, lower aryl or substituted lower aryl.
85. The method of Claim 84 wherein:
R10 is phenyl, tert-butoxy, -S-CH2-CH-(CH3)2, -S-CH(CH3)3, -S-(CH2)3CH3, -O-CH(CH3)3, -NH-CH(CH3)3, -CH=C(CH3)2 or para-chlorophenyl;
R11 is phenyl, (CH3)2CHCH2-, -2-furanyl, cyclopropyl or para-toluyl;
R12 is -H, -OH, CH3CO- or -(CH2)2-N-morpholino;
R13 is methyl, or, R13 and R14, taken together, are -CH2-;
R14 is -H, -CH2SCH3 or -CH2-O-P(O)(OH)2;
R15 is CH3CO-;
R16 is phenyl;
R17 -H, or, R17 and R18, taken together, are -O-CO-O-;
R18 is -H;
R20 is -H or -F; and R21 is -H, -C(O)-CHBr-(CH2)13-CH3 or -C(O)-(CH2)14-CH3; -C(O)-CH2-CH(OH)-COOH, -C(O)-CH2-O-C(O)-CH2CH(NH2)-CONH2, -C(O)-CH2-O--CH2CH2OCH3 or -C(O)-O-C(O)-CH2CH3.
86. The method of Claim 85 wherein the taxol analog is represented by a structure shown in any one of Figures 5-25.
87. The method of Claim 79 wherein the taxol analog is the copolymer of N-(2-hydroxypropyl)methacrylamide,methacryloylglycine-2-hydroxypropylamide and [2aR[2.alpha.,4.beta.,4.beta.,6.beta.,9.alpha.(2R,3S),11.beta.,12.alpha.,12.alp ha.,12.alpha.]]-6,12b-diacetoxy-9-[3-benzamido-2-(methacryloyl-glycyl-L-phenylalanyl-L-leucyl.glycyloxy)-3-phenylpropionyloxy]-12-benzoyloxy-4,11-dihydroxy-4a,8,13,13-tetramethyl-2a,3,4,4a,5,6,9,10,11,12,12a, 12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxet-5-one.
88. The method of Claim 79 wherein the subject is administered taxol or taxotere.
89. The method of Claim 83 wherein the compound is represented by the following structural formula:
wherein Y' is a covalent bond or -CR7R8-.
90. The method of Claim 83 wherein the compound is represented by the following structural formula:
wherein Y" is a covalent bond or -CH2-.
91. The method of Claim 90 wherein R1 and R2 are different and/or R3 and R4 are different.
92. The method of Claim 90 wherein R1 and R2 are the same and R3 and R4 are the same.
93. The method of Claim 92 wherein R3 and R4 are both a lower alkyl group or a substituted lower alkyl group.
94. The method of Claim 93 wherein R3 and R4 are both methyl or ethyl.
95. The method of Claim 94 wherein R1 and R2 are both an aryl or substituted aryl group.
96. The method of Claim 94 wherein R1 and R2 are both a phenyl group or a substituted phenyl group.
97. The method of Claim 94 wherein R1 and R2 are both a phenyl group substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(-NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d-C(=NH)-NHR a, -NR d-C(=NH)-N(R a R b), -NR d-C(=NR c)-NH2, -NR d-C(=NR c)-NHR a, -NR d-C(=NR c)-N(R a R b), -NH-NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c=CR a R b,-CR c=CHR a, -CR c=CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl group, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a-R d are independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d , taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
98. The method of Claim 94 wherein R3 and R4 are both a phenyl group or a substituted phenyl group.
99. The method of Claim 98 wherein R1 and R2 are both a phenyl or substituted phenyl group.
100. The method of Claim 92 wherein R1 and R2 are both a substituted phenyl group.
101. The method of Claim 89 wherein the compound is represented by the following structural formula:

wherein Y' is a covalent bond or -CR7R8-.
102. The method of Claim 101 wherein R7 and R8 are different
103. The method of Claim 101 where R1 and R2 are the same; R3 and R4 are the same;
and R7 and R8 are the same.
104. The method of Claim 101 wherein R1 and R2 are both aryl or substituted aryl groups and R3 and R4 are both a lower alkyl group or a substituted lower alkyl group
105. The method of Claim 101 wherein R1 and R2 are both phenyl or substituted phenyl and R3 and R4 are methyl, ethyl, phenyl, or thienyl.
106. The method of Claim 105 wherein R7 and R8 are both methyl or wherein R7 and R8, taken together, are propylene or butylene.
107. The method of Claim 105 wherein R7 is -H and R8 is lower alkyl, thienyl, phenyl or benzyl.
108. The method of Claim 105 wherein R1 and R2 are both phenyl substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR a, -O-COR a, -COR a, -CN, -No2, -COOH, -So3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH2, -CONHR A, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR C CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, -NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), -NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR d-C(=NH)-NHR a, -NR a-C(=NH)-N(R a R b), -NR d-C(=NR c)-NH2, -NR d-C(=NR c)-NHR a, -NR d-C(=NR c)-N(R a R b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c=CR a R b,-CR c=CHR a, -CR c=CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl groups, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a-R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d , taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
109. A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of taxol or a taxol analog and an effective amount of a compound represented by the following structural formula:
or a physiologically acceptable salt thereof, wherein:
Y' is a covalent bond or -CR7R8-;
R1 and R2 are both a substituted or unsubstituted aryl group;
R3 and R4 are both -H, methyl or ethyl; and R7 is -H and R8 is -H or methyl.
110. The method of Claim 109 wherein R1 and R2 are both phenyl substituted with one or more groups selected from -OH, -Br, -Cl, -I, -F, -OR a, -O-COR a, -COR a, -CN, -NO2, -COOH, -SO3H, -NH2, -NHR a, -N(R a R b), -COOR a, -CHO, -CONH2, -CONHR a, -CON(R a R b), -NHCOR a, -NRCOR a, -NHCONH2, -NHCONR a H, -NHCON(R a R b), -NR c CONH2, -NR c CONR a H, -NR c CON(R a R b), -C(=NH)-NH2, -C(=NH)-NHR a, -C(=NH)-N(R a R b), -C(=NR c)-NH2, -C(=NR c)-NHR a, -C(=NR c)-N(R a R b), -NH-C(=NH)-NH2, NH-C(=NH)-NHR a, -NH-C(=NH)-N(R a R b), NH-C(=NR c)-NH2, -NH-C(=NR c)-NHR a, -NH-C(=NR c)-N(R a R b), -NR d H-C(=NH)-NH2, -NR a-C(=NH)-NHR a, -NR d-C(=NH)-N(R a R b), -NR d-C(NR c)-NH2, -NR d-C(=NR c)-NHR a, -NR d-C(=NR c)-N(R a R b), -NHNH2, -NHNHR a, -NHR a R b, -SO2NH2, -SO2NHR a, -SO2NR a R b, -CH=CHR a, -CH=CR a R b, -CR c=CR a R b,-CR c=CHR a, -CR c=CR a R b, -CCR a, -SH, -SR a, -S(O)R a, -S(O)2R a, alkyl groups, substituted alkyl group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, benzyl group, substituted benzyl group, aryl group or substituted aryl group wherein R a-R d are each independently an alkyl group, substituted alkyl group, benzyl, substituted benzyl, aromatic or substituted aromatic group, or,-NR a R d , taken together, can also form a substituted or unsubstituted non-aromatic heterocyclic group.
111. The method of Claim 89 wherein R5 and R6 are the same.
112. The method of Claim 111 wherein the compound is represented by the following structural formula:

wherein Y" is a covalent bond or -CH2-.
113. The method of Claim 111 wherein R5 and R6 are both a lower alkyl group or a phenyl group.
114. The method of Claim113 wherein R5 and R6 are both a methyl group.
115. The method of Claim 112 wherein R1 and R2 are both phenyl or substituted phenyl; R3 and R4 are both a lower alkyl group; and R5 and R6 are both a lower alkyl group.
116. A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of taxol or a taxol analog and an effective amount of a compound represented by the following structural formula:

or physiologically acceptable salt thereof, wherein:

a) R1 and R2 are both phenyl; R3 and R4 are both phenyl; R7 and R8 are both -H;
b) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
c) R1 and R2 are both phenyl; R3 and R4 are both ethyl; R7 and R8 are both -H;
d) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
e) R1 and R2 are both 4-methoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 is methyl;R8 is -H;
g) R1 and R2 are both phenyl; R3 and R4 are both ethyl; R7 is methyl; R8 is -H;
h) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
i) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
j) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
k) R1 arid R2 are both 3-cyanophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
l) R1 and R2 are both 3-fluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
m) R1 and R2 are both 4-chlorophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
n) R1 and R2 are both 2-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
o) R1 and R2 are both 3-methoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
p) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
q) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
r) R1 and R2 are both 2,5-difluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;

s) R1 and R2 are both 2,5-difluorophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
t) R1 and R2 are both 2,5-dichlorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
u) R1 and R2 are both 2,5-dimethylphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
v) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
w) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H; and x) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H.
117. A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of taxol or a taxol analog and an effective amount of a compound represented by the following structural formula:

or a physiologically acceptable salt thereof, wherein:
a) R1 and R2 are both 4-cyanophenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
b) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
c) R1 and R2 are both 2,5-dimethoxyphenyl; R3 and R4 are both methyl; R7 is methyl; R8 is -H;
d) R1 and R2 are both 3-fluorophenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
e) R1 and R2 are both 2,3-dimethoxyphenyl; R3 and R4 are both methyl; R7 and R8 are both -H;
f) R1 and R2 are both phenyl; R3 and R4 are both methyl; R7 and R8 are both -H; and g) R1 and R2 are both phenyl; R3 and R4 are both phenyl; R7 and R8 are both -H.
CA2455453A 2001-07-10 2002-07-10 Taxol enhancer compounds Expired - Fee Related CA2455453C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US30425201P 2001-07-10 2001-07-10
US60/304,252 2001-07-10
US36194602P 2002-03-06 2002-03-06
US60/361,946 2002-03-06
PCT/US2002/021717 WO2003006430A1 (en) 2001-07-10 2002-07-10 Taxol enhancer compounds

Publications (2)

Publication Number Publication Date
CA2455453A1 true CA2455453A1 (en) 2003-01-23
CA2455453C CA2455453C (en) 2011-02-15

Family

ID=26973915

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2455453A Expired - Fee Related CA2455453C (en) 2001-07-10 2002-07-10 Taxol enhancer compounds

Country Status (24)

Country Link
US (6) US6800660B2 (en)
EP (3) EP1406869B1 (en)
JP (1) JP4344235B2 (en)
KR (2) KR100990581B1 (en)
CN (1) CN100348580C (en)
AT (2) ATE339402T1 (en)
AU (1) AU2002316626B2 (en)
BR (1) BR0211227A (en)
CA (1) CA2455453C (en)
CY (1) CY1105811T1 (en)
DE (1) DE60214718T2 (en)
DK (2) DK1731148T3 (en)
ES (2) ES2271292T3 (en)
HK (2) HK1060115A1 (en)
IL (2) IL159773A0 (en)
IS (1) IS2412B (en)
MX (1) MXPA04000244A (en)
NO (1) NO329457B1 (en)
NZ (1) NZ530963A (en)
PT (1) PT1406869E (en)
SI (1) SI1406869T1 (en)
TW (1) TWI332943B (en)
WO (1) WO2003006430A1 (en)
ZA (1) ZA200401051B (en)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6924312B2 (en) * 2001-07-10 2005-08-02 Synta Pharmaceuticals Corp. Taxol enhancer compounds
TWI252847B (en) 2001-07-10 2006-04-11 Synta Pharmaceuticals Corp Synthesis of taxol enhancers
TWI332943B (en) * 2001-07-10 2010-11-11 Synta Pharmaceuticals Corp Taxol enhancer compounds
TWI297335B (en) * 2001-07-10 2008-06-01 Synta Pharmaceuticals Corp Taxol enhancer compounds
TWI330079B (en) 2003-01-15 2010-09-11 Synta Pharmaceuticals Corp Treatment for cancers
AU2006228035B2 (en) * 2003-01-15 2010-02-18 Synta Pharmaceuticals Corp. Bis (thio-hydrazide amide) compounds for treating multi-drug resistant cancer
WO2006009940A1 (en) * 2004-06-23 2006-01-26 Synta Pharmaceuticals Corp. Bis(thio-hydrazide amide) salts for treatment of cancers
US20060142393A1 (en) * 2004-09-16 2006-06-29 Sherman Matthew L Bis(thio-hydrazide amides) for treatment of hyperplasia
JP5204489B2 (en) * 2004-11-19 2013-06-05 シンタ ファーマスーティカルズ コーポレイション Bis (thio-hydrazide amide) to increase HSP70 expression
US20060167106A1 (en) * 2004-11-19 2006-07-27 Mei Zhang Compounds acting at the centrosome
CA2604907A1 (en) 2005-04-15 2006-10-26 Synta Pharmaceuticals Corp. Combination cancer therapy with bis(thiohydrazide) amide compounds
WO2006113572A1 (en) * 2005-04-15 2006-10-26 Synta Pharmaceuticals Corp. Methods of increasing natural killer cell activity for therapy
MX2007014314A (en) * 2005-05-16 2008-02-11 Synta Pharmaceuticals Corp Synthesis of bis(thio-hydrazide amide) salts.
KR20080035642A (en) * 2005-08-16 2008-04-23 신타 파마슈티칼스 코프. Bis(thio-hydrazide amide) formulation
TW200804307A (en) * 2005-10-27 2008-01-16 Synta Pharmaceuticals Corp Process for preparing mesylate salts of IL-12 inhibitory compounds
JP2010501558A (en) * 2006-08-21 2010-01-21 シンタ ファーマシューティカルズ コーポレーション Combination with bis (thiohydrazide amide) to treat cancer
JP2010501564A (en) * 2006-08-21 2010-01-21 シンタ ファーマシューティカルズ コーポレーション Bis (thiohydrazide amide) for treating melanoma
JP2010501559A (en) * 2006-08-21 2010-01-21 シンタ ファーマシューティカルズ コーポレーション Bis (thiohydrazide amide) for use in preventing or delaying melanoma recurrence
US8785451B2 (en) * 2006-08-21 2014-07-22 Synta Pharmaceuticals Corp. Compounds for the treatment of proliferative disorders
EP2074097A2 (en) 2006-08-21 2009-07-01 Synta Pharmaceuticals Corporation Compounds for treating proliferative disorders
MX2009001877A (en) 2006-08-21 2009-03-02 Synta Pharmaceuticals Corp Compounds for treating proliferative disorders.
AU2007290490B2 (en) 2006-08-31 2011-09-08 Synta Pharmaceuticals Corp. Combination with bis(thiohydrazide amides) for treating cancer
EP2061430A2 (en) * 2006-09-11 2009-05-27 Synta Pharmaceuticals Corporation Bis (thiohydrazide amides) formulation
US9498528B2 (en) * 2006-09-13 2016-11-22 Genzyme Corporation Treatment of multiple sclerosis (MS)
TW200829543A (en) * 2006-09-15 2008-07-16 Synta Pharmaceuticals Corp Purification of bis(thiohydrazide amides)
WO2008082579A1 (en) * 2007-01-03 2008-07-10 Synta Pharmaceuticals Corp. Method for treating cancer
WO2008136976A2 (en) * 2007-04-30 2008-11-13 Synta Pharmaceuticals Corp. Compounds for treating proliferative disorders
WO2009020631A2 (en) 2007-08-07 2009-02-12 Synta Pharmaceuticals Corp. Compounds for treating proliferative disorders
US8618170B2 (en) * 2007-11-09 2013-12-31 Synta Pharmaceuticals Corp. Oral formulations of bis(thiohydrazide amides)
TW200940050A (en) * 2007-11-28 2009-10-01 Synta Pharmaceuticals Corp Polymorphs of N-malonyl-bis(N'-methyl-N'-thiobenzoylhydrazide)
WO2009073148A2 (en) * 2007-11-28 2009-06-11 Synta Pharmaceuticals Corp. Polymorphs of n-malonyl-bis(n'-methyl-n'-thiobenzoylhydrazide)
US8581004B2 (en) 2008-02-21 2013-11-12 Synta Pharmaceuticals Corp. Compounds for treating proliferative disorders
WO2009123704A2 (en) * 2008-03-31 2009-10-08 Synta Pharmaceuticals Corp. Process for preparing bis(thiohydrazide amides)
WO2010048293A1 (en) * 2008-10-22 2010-04-29 Synta Pharmaceuticals Corp. Transition metal complexes of a bis[thiohydrazide amide] compound
JP2012506443A (en) 2008-10-22 2012-03-15 シンタ ファーマシューティカルズ コーポレーション Transition metal complexes of bis [thiohydrazide amide] compounds
US8525776B2 (en) * 2008-10-27 2013-09-03 Lenovo (Singapore) Pte. Ltd Techniques for controlling operation of a device with a virtual touchscreen
AU2009322603B2 (en) 2008-12-01 2013-08-29 Synta Pharmaceuticals Corp. Compounds for treating proliferative disorders
WO2011069159A2 (en) 2009-12-04 2011-06-09 Synta Pharmaceuticals Corp. Bis[thiohydrazide amide] compounds for treating leukemia
WO2011133673A1 (en) 2010-04-20 2011-10-27 Synta Pharmaceuticals Corp. Use of bis [thiohydrazide amide] compounds such as elesclomol for treating cancers
US20140329892A1 (en) 2011-11-10 2014-11-06 Synta Pharmaceuticals Corp. Administration of a bis(thiohydrazide amide) compound for treating cancers
US20130149392A1 (en) * 2011-12-12 2013-06-13 Synta Pharmaceuticals Corp. Method of treating non-small cell lung cancer with bis-(thiohydrazide)amide compounds
US20150057357A1 (en) 2012-01-05 2015-02-26 The Board Of Trustees Of The Leland Stanford Junior University Bis (thiohydrazide amide) compounds for treating cancers

Family Cites Families (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US304318A (en) 1884-09-02 Inlet-pipe for water-works
US304252A (en) 1884-08-26 Gael behee
US361946A (en) 1887-04-26 Watch arbor and pivot
US3357956A (en) * 1965-03-30 1967-12-12 Du Pont Polymeric 1, 3, 4-thiadiazoles and the process for their preparation
FR2097737A5 (en) 1970-07-14 1972-03-03 Berlin Chemie Veb Virustatic 4-substd 1-acylthiosemicarbazides -from carboxylic acid - hydrazide and isothiocyanates or from carboxylic acid chloride and 4-
DE2037257A1 (en) 1970-07-28 1972-02-03 Farbwerke Hoechst AG, vorm. Meister Lucius & Brüning, 6000 Frankfurt Poly-(5-amino-1,3,4-thiadiazol-2-yl) derivs prepn - intermediates for drug and polymer prodn
GB1272920A (en) 1971-03-15 1972-05-03 Berlin Chemie Veb New thiosemicarbazides
US4012360A (en) * 1973-12-03 1977-03-15 Ciba-Geigy Corporation Bis-salicyloyl-dicarboxylic acid dihydrazides as stabilizers for polyolefines
JPS5091056A (en) * 1973-12-17 1975-07-21
US4822777A (en) 1987-02-27 1989-04-18 Liposome Technology, Inc. Amphotericin B/cholesterol sulfate composition
JP2767241B2 (en) 1987-04-15 1998-06-18 ロ−ム アンド ハ−ス コンパニ− Pesticidal N- (optionally substituted) -N'-substituted-N, N'-disubstituted hydrazines
US6013836A (en) * 1992-02-28 2000-01-11 Rohm And Haas Company Insecticidal N'-substituted-N,N'-disubstitutedhydrazines
FR2697752B1 (en) * 1992-11-10 1995-04-14 Rhone Poulenc Rorer Sa Antitumor compositions containing taxane derivatives.
US6753006B1 (en) 1993-02-22 2004-06-22 American Bioscience, Inc. Paclitaxel-containing formulations
BR9405798A (en) 1993-02-22 1995-12-12 Vivorx Pharmaceuticals Inc Methods for in vivo release of biological material and useful compositions thereof
US5665382A (en) 1993-02-22 1997-09-09 Vivorx Pharmaceuticals, Inc. Methods for the preparation of pharmaceutically active agents for in vivo delivery
US5916596A (en) 1993-02-22 1999-06-29 Vivorx Pharmaceuticals, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
US6096331A (en) 1993-02-22 2000-08-01 Vivorx Pharmaceuticals, Inc. Methods and compositions useful for administration of chemotherapeutic agents
US6749868B1 (en) 1993-02-22 2004-06-15 American Bioscience, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
US6537579B1 (en) 1993-02-22 2003-03-25 American Bioscience, Inc. Compositions and methods for administration of pharmacologically active compounds
US5439686A (en) 1993-02-22 1995-08-08 Vivorx Pharmaceuticals, Inc. Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor
US5840746A (en) 1993-06-24 1998-11-24 Merck Frosst Canada, Inc. Use of inhibitors of cyclooxygenase in the treatment of neurodegenerative diseases
US5523325A (en) 1993-09-09 1996-06-04 Jacobson; Richard M. Amidrazones and their use as pesticides
WO1995033710A1 (en) 1994-06-03 1995-12-14 Basf Aktiengesellschaft Carbamoyl carboxylic acid hydrazides and their use against fungi
AU4482996A (en) * 1995-09-22 1997-04-09 Novo Nordisk A/S Novel variants of green fluorescent protein, gfp
US5739686A (en) 1996-04-30 1998-04-14 Naughton; Michael J. Electrically insulating cantilever magnetometer with mutually isolated and integrated thermometry, background elimination and null detection
KR980008219A (en) 1996-07-16 1998-04-30 김상응 Pharmaceutical composition for stabilized injection
KR100529512B1 (en) * 1997-04-18 2005-11-22 얀센 파마슈티카 엔.브이. Use of 5HT3 antagonists for promoting intestinal lavage
US6235787B1 (en) * 1997-06-30 2001-05-22 Hoffmann-La Roche Inc. Hydrazine derivatives
GB9727524D0 (en) * 1997-12-31 1998-02-25 Pharmacia & Upjohn Spa Synergistic antitumor composition containing a biologically active ureido compound
JP3099880B2 (en) * 1998-08-12 2000-10-16 日本電気株式会社 Semiconductor switch and switch circuit
TW479053B (en) * 1998-10-19 2002-03-11 Agro Kanesho Co Ltd Hydrazineoxoacetamide derivatives and pesticides
ES2161594B1 (en) * 1998-12-17 2003-04-01 Servier Lab NEW DERIVATIVES OF HYDRAZIDE, ITS PREPARATION PROCEDURE AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
JP3908876B2 (en) * 1999-07-23 2007-04-25 日東電工株式会社 Base film for adhesive tape and adhesive tape or sheet
US6322303B1 (en) * 2000-05-12 2001-11-27 David M. John Dunnage bag and method of making same
EP1164126A1 (en) * 2000-06-16 2001-12-19 Basf Aktiengesellschaft Salicylic acid hydrazide derivatives, process and intermediates for their preparation, agents containing them and their use for combatting damaging fungi
US6365745B1 (en) * 2000-07-14 2002-04-02 Sumika Fine Chemicals Co., Ltd. Method for producing hydrazine derivative
MXPA03006666A (en) * 2001-01-25 2004-05-31 Guilford Pharm Inc Trisubstituted carbocyclic cyclophilin binding compounds and their use.
US20020198160A1 (en) 2001-05-01 2002-12-26 Everitt Elizabeth A. Compositions and methods for enhancing the bioavailability of pharmaceutical agents
EP1387678A1 (en) 2001-05-03 2004-02-11 Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften E.V. Compounds that inhibit hsp90 and stimulate hsp70 and hsp40, useful in the prevention or treatment of diseases associated with protein aggregation and amyloid formation
US6602907B1 (en) * 2001-06-08 2003-08-05 University Of Central Florida Treatment of breast cancer
US6924312B2 (en) * 2001-07-10 2005-08-02 Synta Pharmaceuticals Corp. Taxol enhancer compounds
TWI252847B (en) 2001-07-10 2006-04-11 Synta Pharmaceuticals Corp Synthesis of taxol enhancers
TWI332943B (en) * 2001-07-10 2010-11-11 Synta Pharmaceuticals Corp Taxol enhancer compounds
TWI297335B (en) 2001-07-10 2008-06-01 Synta Pharmaceuticals Corp Taxol enhancer compounds
WO2003045926A1 (en) 2001-11-28 2003-06-05 Societe De Conseils De Recherche Et D'applications Scientifiques (S.C.R.A.S.) 5-sulphanyl-4h-1,2,4-triazole derivatives and their use as medicine
TW200408407A (en) 2001-11-30 2004-06-01 Dana Farber Cancer Inst Inc Methods and compositions for modulating the immune system and uses thereof
TWI330079B (en) 2003-01-15 2010-09-11 Synta Pharmaceuticals Corp Treatment for cancers
AU2006228035B2 (en) 2003-01-15 2010-02-18 Synta Pharmaceuticals Corp. Bis (thio-hydrazide amide) compounds for treating multi-drug resistant cancer
KR101166749B1 (en) 2003-02-11 2012-07-27 베르날리스(캠브리지)리미티드 Isoxazole compounds as inhibitors of heat shock proteins
KR100575251B1 (en) 2003-03-03 2006-05-02 재단법인서울대학교산학협력재단 Pharmaceutical composition for treatment of cancer containing p38/JTV-1 as an effective component and screening method for pharmaceutical composition for treatment of cancer
EP1493445A1 (en) 2003-07-04 2005-01-05 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Inhibition of stress-induced ligand-dependent EGFR activation
AR045595A1 (en) 2003-09-04 2005-11-02 Vertex Pharma USEFUL COMPOSITIONS AS INHIBITORS OF KINASE PROTEINS
KR100544347B1 (en) 2003-12-11 2006-01-23 한국생명공학연구원 Pharmaceutical compositions of diaryl-isoxazole compounds for the prevention and treatment of cancers
JP2007530589A (en) 2004-03-26 2007-11-01 アンフォラ ディスカバリー コーポレーション Certain triazole-based compounds, compositions, and uses thereof
WO2006009940A1 (en) 2004-06-23 2006-01-26 Synta Pharmaceuticals Corp. Bis(thio-hydrazide amide) salts for treatment of cancers
US7385085B2 (en) * 2004-07-09 2008-06-10 Elan Pharmaceuticals, Inc. Oxime derivative substituted hydroxyethylamine aspartyl protease inhibitors
US20060142393A1 (en) 2004-09-16 2006-06-29 Sherman Matthew L Bis(thio-hydrazide amides) for treatment of hyperplasia
JP5204489B2 (en) 2004-11-19 2013-06-05 シンタ ファーマスーティカルズ コーポレイション Bis (thio-hydrazide amide) to increase HSP70 expression
US20060167106A1 (en) 2004-11-19 2006-07-27 Mei Zhang Compounds acting at the centrosome
AU2006214164B2 (en) 2005-02-17 2010-12-09 Synta Pharmaceuticals Corp. Isoxazole combretastin derivatives for the treatment of disorders
WO2006113493A2 (en) 2005-04-15 2006-10-26 Synta Pharmaceuticals Corp. Methods of determining cancer prognosis via natural killer cell activity
CA2604907A1 (en) 2005-04-15 2006-10-26 Synta Pharmaceuticals Corp. Combination cancer therapy with bis(thiohydrazide) amide compounds
WO2006113572A1 (en) 2005-04-15 2006-10-26 Synta Pharmaceuticals Corp. Methods of increasing natural killer cell activity for therapy
MX2007014314A (en) 2005-05-16 2008-02-11 Synta Pharmaceuticals Corp Synthesis of bis(thio-hydrazide amide) salts.
KR20080035642A (en) 2005-08-16 2008-04-23 신타 파마슈티칼스 코프. Bis(thio-hydrazide amide) formulation
JP5441690B2 (en) 2006-05-25 2014-03-12 シンタ ファーマシューティカルズ コーポレーション Triazole compounds that modulate Hsp90 activity
WO2008024298A1 (en) 2006-08-21 2008-02-28 Synta Pharmaceuticals Corp. Bis(thiohydrazide amides) for inhibiting angiogenesis
MX2009001877A (en) 2006-08-21 2009-03-02 Synta Pharmaceuticals Corp Compounds for treating proliferative disorders.
JP2010501559A (en) 2006-08-21 2010-01-21 シンタ ファーマシューティカルズ コーポレーション Bis (thiohydrazide amide) for use in preventing or delaying melanoma recurrence
JP2010501564A (en) 2006-08-21 2010-01-21 シンタ ファーマシューティカルズ コーポレーション Bis (thiohydrazide amide) for treating melanoma
JP2010501558A (en) 2006-08-21 2010-01-21 シンタ ファーマシューティカルズ コーポレーション Combination with bis (thiohydrazide amide) to treat cancer
EP2074097A2 (en) 2006-08-21 2009-07-01 Synta Pharmaceuticals Corporation Compounds for treating proliferative disorders
AU2007290490B2 (en) 2006-08-31 2011-09-08 Synta Pharmaceuticals Corp. Combination with bis(thiohydrazide amides) for treating cancer
EP2061430A2 (en) 2006-09-11 2009-05-27 Synta Pharmaceuticals Corporation Bis (thiohydrazide amides) formulation
EP2059250A2 (en) 2006-09-14 2009-05-20 Synta Pharmaceuticals Corporation Compounds for the treatment of angiogenesis
TW200829543A (en) 2006-09-15 2008-07-16 Synta Pharmaceuticals Corp Purification of bis(thiohydrazide amides)
WO2008082579A1 (en) 2007-01-03 2008-07-10 Synta Pharmaceuticals Corp. Method for treating cancer
WO2008136976A2 (en) 2007-04-30 2008-11-13 Synta Pharmaceuticals Corp. Compounds for treating proliferative disorders
WO2009020631A2 (en) 2007-08-07 2009-02-12 Synta Pharmaceuticals Corp. Compounds for treating proliferative disorders
US8618170B2 (en) 2007-11-09 2013-12-31 Synta Pharmaceuticals Corp. Oral formulations of bis(thiohydrazide amides)
TW200940050A (en) 2007-11-28 2009-10-01 Synta Pharmaceuticals Corp Polymorphs of N-malonyl-bis(N'-methyl-N'-thiobenzoylhydrazide)
WO2009073148A2 (en) 2007-11-28 2009-06-11 Synta Pharmaceuticals Corp. Polymorphs of n-malonyl-bis(n'-methyl-n'-thiobenzoylhydrazide)

Also Published As

Publication number Publication date
US9107955B2 (en) 2015-08-18
IL159773A (en) 2011-11-30
CN100348580C (en) 2007-11-14
JP4344235B2 (en) 2009-10-14
US20060122183A1 (en) 2006-06-08
US7671092B2 (en) 2010-03-02
NO329457B1 (en) 2010-10-25
ATE339402T1 (en) 2006-10-15
ES2271292T3 (en) 2007-04-16
MXPA04000244A (en) 2005-03-07
KR101060079B1 (en) 2011-08-29
ZA200401051B (en) 2005-08-31
PT1406869E (en) 2007-01-31
KR20040077650A (en) 2004-09-06
DE60214718D1 (en) 2006-10-26
TWI332943B (en) 2010-11-11
NO20040095L (en) 2004-02-23
JP2004534848A (en) 2004-11-18
SI1406869T1 (en) 2007-02-28
ES2395193T3 (en) 2013-02-11
AU2002316626B2 (en) 2005-06-02
EP1406869B1 (en) 2006-09-13
CN1553895A (en) 2004-12-08
US20150344420A1 (en) 2015-12-03
US20080214655A1 (en) 2008-09-04
US7037940B2 (en) 2006-05-02
US20030119914A1 (en) 2003-06-26
EP1731148A1 (en) 2006-12-13
IL159773A0 (en) 2004-06-20
KR20100066588A (en) 2010-06-17
KR100990581B1 (en) 2010-10-29
NZ530963A (en) 2005-08-26
US20050009920A1 (en) 2005-01-13
DK1731148T3 (en) 2012-02-27
DE60214718T2 (en) 2007-09-13
HK1060115A1 (en) 2004-07-30
WO2003006430A1 (en) 2003-01-23
ATE533483T1 (en) 2011-12-15
IS7101A (en) 2004-01-09
EP1731148B1 (en) 2011-11-16
EP2289876A1 (en) 2011-03-02
CA2455453C (en) 2011-02-15
US7345094B2 (en) 2008-03-18
CY1105811T1 (en) 2011-02-02
HK1101543A1 (en) 2007-10-18
EP1406869A1 (en) 2004-04-14
US6800660B2 (en) 2004-10-05
DK1406869T3 (en) 2007-01-22
US20100280075A1 (en) 2010-11-04
BR0211227A (en) 2004-08-10
IS2412B (en) 2008-10-15

Similar Documents

Publication Publication Date Title
CA2455453A1 (en) Taxol enhancer compounds
CA2454120A1 (en) Taxol enhancer compounds
CA2512797A1 (en) Bis (thio-hydrazide amide) compounds for treating multi-drug resistant cancer
RU2003120080A (en) ORTHO-SUBSTITUTED NITROGEN-CONTAINING BISARYL COMPOUNDS FOR APPLICATION AS POTASSIUM CHANNEL INHIBITORS, AND ALSO CONTAINING THEIR PHARMACEUTICAL COMPOSITIONS
AU2002316626A1 (en) Taxol enhancer compounds
JP2004534846A5 (en)
RU2002101723A (en) INDANYL SUBSTITUTED BENZENE CARBONAMIDES, METHOD FOR PRODUCING THEM, THEIR USE AS A MEDICINAL PRODUCT, AND ALSO CONTAINING THEIR PHARMACEUTICAL COMPOSITIONS
RU2003121236A (en) AILATED AMIDES OF FURAN- AND THIOPHENCARBOXYLIC ACIDS WITH LOCKING POTASSIUM CHANNEL ACTION
JP2004531517A5 (en)
RU2003134544A (en) AMRIDES OF ANTRANILIC ACID, METHODS FOR PRODUCING THEM, THEIR APPLICATION AS ANTIARRHYTHMIC MEDICINES, AND ALSO CONTAINING THEIR PHARMACEUTICAL COMPOSITIONS
JP2004534848A5 (en)
KR970025611A (en) Substituted sulfonimidamides, methods for their preparation, their use as pharmaceuticals or diagnostic agents, and pharmaceuticals containing the same
RU2005121146A (en) HYDROXYETHYLAMINE DERIVATIVES FOR TREATMENT OF ALZHEIMER'S DISEASE
BR9808481A (en) Compound 2-aminopropane-1,3-diol, its pharmaceutical use and synthetic intermediates for the same
RU2001104339A (en) Thiobenzimidazole derivatives
TNSN02039A1 (en) RECONSTITUTABLE PARENTERAL COMPOSITION
KR950014067A (en) Arylamide derivatives
RU2005133665A (en) APPLICATION OF 10-HYDROXY-10,11-DIHYDROCARBAMAZEPINE DERIVATIVES FOR THE TREATMENT OF AFFECTIVE DISORDERS
KR910002445A (en) Use of 5-heteroaryl- or 5-aryl-substituted imidazo [2,1-a] isoquinoline
RU2003109440A (en) Derivatives of 5-amidino-2-hydroxybenzenesulfonamide containing their pharmaceutical compositions and intermediates for their preparation
RU2006104024A (en) KAPPA-AGONISTS, ESPECIALLY FOR TREATMENT AND / OR PREVENTION OF AN IRRITATED FATIGUE SYNDROME
MX9405111A (en) NEW DERIVATIVES OF (1-PHENYL-1-HETEROCICLIL) METHANOL AND (1-PHENYL-1-HETEROCICLIL-METHYLAMINE).
JPH09151137A (en) Medicine for inhibiting multiplication of smooth muscle cell
KR970703316A (en) 4-quinolinone derivative or salt thereof (4-QUINOLINONE DERIVATIVE OR SALT THEREOF)

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20170710