CA2340636A1 - Combinations of tetracyclic cyclic gmp-specific phosphodiesterase inhibitors with further therapeutic agents - Google Patents

Combinations of tetracyclic cyclic gmp-specific phosphodiesterase inhibitors with further therapeutic agents Download PDF

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Publication number
CA2340636A1
CA2340636A1 CA002340636A CA2340636A CA2340636A1 CA 2340636 A1 CA2340636 A1 CA 2340636A1 CA 002340636 A CA002340636 A CA 002340636A CA 2340636 A CA2340636 A CA 2340636A CA 2340636 A1 CA2340636 A1 CA 2340636A1
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Canada
Prior art keywords
3alkyl
ring
represents hydrogen
specific phosphodiesterase
combinations
Prior art date
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Granted
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CA002340636A
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French (fr)
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CA2340636C (en
Inventor
Alain Claude-Marie Daugan
Francoise Gellibert
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Icos Corp
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Icos Corporation
Alain Claude-Marie Daugan
Francoise Gellibert
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Publication of CA2340636A1 publication Critical patent/CA2340636A1/en
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Publication of CA2340636C publication Critical patent/CA2340636C/en
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed systems

Abstract

A compound of formula (I) and salts and solvates thereof, in which: R0 represents hydrogen, halogen, or C1-6alkyl; R1 represents hydrogen, C1-6-alkyl, C2-6alkenyl, C2-6alkynyl, haloC1-6alkyl, C3-8cycloalkyl, C3-8cyloalkylC1-3alkyl, arylC1-3alkyl, or heteroarylC1-3alkyl; R2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan, and pyridine, or an optionally substituted bicyclic ring (a) attached to the rest of the molecule via one of the benzene ring carbon atoms, and wherein the fused ring (A) is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated, and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur, and nitrogen;
and R3 represents hydrogen or C1-3alkyl, or R1 and R3 together represent a 3- or 4-membered alkyl or alkenyl chain. A compound of formula (I) is a potent and selective inhibitor of cyclic guanosine 3', 5'-monophosphate specific phosphodiesterase (cGMP specific PDE) having a utility in a variety of therapeutic areas where such inhibition is beneficial, including the treatment of cardiovascular disorders and erectile dysfunction.
CA002340636A 1998-09-16 1999-08-26 Combinations of tetracyclic cyclic gmp-specific phosphodiesterase inhibitors with further therapeutic agents Expired - Fee Related CA2340636C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/154,051 US6143746A (en) 1994-01-21 1998-09-16 Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use
US09/154,051 1998-09-16
PCT/US1999/019466 WO2000015228A1 (en) 1998-09-16 1999-08-26 Combinations of tetracyclic cyclic gmp-specific phosphodiesterase inhibitors with further therapeutic agents

Publications (2)

Publication Number Publication Date
CA2340636A1 true CA2340636A1 (en) 2000-03-23
CA2340636C CA2340636C (en) 2007-08-07

Family

ID=22549790

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002340636A Expired - Fee Related CA2340636C (en) 1998-09-16 1999-08-26 Combinations of tetracyclic cyclic gmp-specific phosphodiesterase inhibitors with further therapeutic agents

Country Status (7)

Country Link
US (1) US6143746A (en)
EP (3) EP2327408A1 (en)
JP (1) JP2002524516A (en)
AU (1) AU5785699A (en)
BR (1) BR9913824A (en)
CA (1) CA2340636C (en)
WO (1) WO2000015228A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018188446A1 (en) * 2017-04-14 2018-10-18 中山大学 Evodiamine compounds, preparation method therefor and application thereof

Families Citing this family (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060222647A1 (en) * 1993-05-27 2006-10-05 Beavo Joseph A Methods and compositions for modulating the activity of PDE5
US6143746A (en) * 1994-01-21 2000-11-07 Icos Corporation Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use
US6331543B1 (en) 1996-11-01 2001-12-18 Nitromed, Inc. Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use
DK1049695T3 (en) * 1997-11-12 2002-05-13 Bayer Ag 2-Phenyl-substituted imidazotriazinones as phosphodiesterase inhibitors
GB9801398D0 (en) 1998-01-22 1998-03-18 Anggard Erik E Chemical compounds
CZ20021151A3 (en) 1999-10-11 2003-03-12 Pfizer Inc. 5-(2-substituted-5-heterocyclyl sulfonylpyrid-3-yl)-dihydropyrazolo[4,3-d]-pyrimidin-7-ones functioning as phosphodiesterase inhibitors
IL139456A0 (en) 1999-11-08 2001-11-25 Pfizer Compounds for the treatment of female sexual dysfunction
US20020013327A1 (en) * 2000-04-18 2002-01-31 Lee Andrew G. Compositions and methods for treating female sexual dysfunction
CN1630532A (en) * 2000-04-19 2005-06-22 约翰斯霍普金斯大学 Methods for prevention and treatment of gastrointestinal disorders
WO2001094347A1 (en) * 2000-06-08 2001-12-13 Lilly Icos Llc Tetracyclic diketopiperazine compounds as pdev inhibitors
ATE300543T1 (en) * 2000-06-26 2005-08-15 Lilly Icos Llc CONDENSED PYRAZINEDIONE DERIVATIVES AS PDE5 INHIBITERS
US6503894B1 (en) 2000-08-30 2003-01-07 Unimed Pharmaceuticals, Inc. Pharmaceutical composition and method for treating hypogonadism
US6821978B2 (en) * 2000-09-19 2004-11-23 Schering Corporation Xanthine phosphodiesterase V inhibitors
DE10058663A1 (en) * 2000-11-25 2002-05-29 Merck Patent Gmbh Use of thienopyrimidines
CA2431074A1 (en) * 2000-12-19 2002-06-27 Merck Patent Gesellschaft Mit Beschraenkter Haftung Pharmaceutical formulation comprising thienopyrimidines and antithrombotics, calcium antagonists, prostaglandins or prostaglandin derivatives (1)
EP1347762A2 (en) * 2000-12-19 2003-10-01 MERCK PATENT GmbH Pharmaceutical formulation containing thienopyrimidines and antithrombotics, calcium antagonists, prostaglandins or prostaglandin derivatives (2)
SK8192003A3 (en) * 2000-12-19 2003-10-07 Merck Patent Gmbh Pharmaceutical formulation containing pyrazolo[4,3-d]pyrimidines and antithrombotic agents, calcium-antagonists, prostaglandins or prostaglandin derivatives
EP1392314B1 (en) * 2001-05-09 2006-12-20 Bayer HealthCare AG NOVEL USE OF 2-[2-Ethoxy-5-(4-methyl-piperazin-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-on
US20070122353A1 (en) 2001-05-24 2007-05-31 Hale Ron L Drug condensation aerosols and kits
US7458374B2 (en) 2002-05-13 2008-12-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US7645442B2 (en) 2001-05-24 2010-01-12 Alexza Pharmaceuticals, Inc. Rapid-heating drug delivery article and method of use
US7766013B2 (en) 2001-06-05 2010-08-03 Alexza Pharmaceuticals, Inc. Aerosol generating method and device
MXPA03011167A (en) * 2001-06-21 2004-02-26 Lilly Icos Llc Carboline derivatives as pdev inhibitors.
DE10135815A1 (en) * 2001-07-23 2003-02-06 Bayer Ag Use of imidazo-triazinone derivative phosphodiesterase 5 inhibitors e.g. for treatment of cardiac insufficiency, psoriasis, diabetes, cancer, glaucoma, bladder disease, Parkinson's disease or pain
WO2003013432A2 (en) * 2001-08-10 2003-02-20 Nitromed, Inc. Methods of use for novel sulfur containing organic nitrate compounds
US6479493B1 (en) 2001-08-23 2002-11-12 Cell Pathways, Inc. Methods for treatment of type I diabetes
EP1442042A1 (en) * 2001-11-09 2004-08-04 Schering Corporation Polycyclic guanine derivative phosphodiesterase v inhibitors
US6686349B2 (en) 2001-11-14 2004-02-03 Ortho-Mcneil Pharmaceutical, Inc. Substituted tetracyclic pyrroloquinolone derivatives useful as phosphodiesterase inhibitors
CA2469075C (en) * 2001-12-20 2011-09-13 Applied Research Systems Ars Holding N.V. Pyrrolidine derivatives as prostaglandin modulators
US20030216407A1 (en) * 2002-01-31 2003-11-20 Pfizer Inc. Use of PDE5 inhibitors in the treatment of scarring
JP2005529927A (en) * 2002-05-23 2005-10-06 ファイザー インコーポレイテッド New combination
DE10232113A1 (en) * 2002-07-16 2004-01-29 Bayer Ag Medicinal products containing vardenafil hydrochloride trihydrate
US6531162B1 (en) * 2002-07-30 2003-03-11 William Charles Llewellyn Adrenergically-mediated weight loss product
US8133903B2 (en) * 2003-10-21 2012-03-13 Los Angeles Biomedical Research Institute at Harbor—UCLA Medical Center Methods of use of inhibitors of phosphodiesterases and modulators of nitric oxide, reactive oxygen species, and metalloproteinases in the treatment of peyronie's disease, arteriosclerosis and other fibrotic diseases
US20040105818A1 (en) 2002-11-26 2004-06-03 Alexza Molecular Delivery Corporation Diuretic aerosols and methods of making and using them
US7913688B2 (en) 2002-11-27 2011-03-29 Alexza Pharmaceuticals, Inc. Inhalation device for producing a drug aerosol
KR20070091049A (en) 2002-12-13 2007-09-06 워너-램버트 캄파니 엘엘씨 Alpha-2-delta ligand to treat lower urinary tract symptoms
US20050048573A1 (en) * 2003-02-03 2005-03-03 Plexxikon, Inc. PDE5A crystal structure and uses
WO2005079808A1 (en) 2004-01-22 2005-09-01 Pfizer Limited Triazole derivatives which inhibit vasopressin antagonistic activity
EP1742932A1 (en) * 2004-04-28 2007-01-17 Pfizer Limited 3-heterocyclyl-4-phenyl-triazole derivatives as inhibitors of the vasopressin v1a receptor
DE102004023069A1 (en) * 2004-05-11 2005-12-08 Bayer Healthcare Ag New dosage forms of the PDE 5 inhibitor vardenafil
US20060083724A1 (en) * 2004-10-01 2006-04-20 Hilst Todd W Compositions for the treatment of femal sexual dysfunction
DE102005001989A1 (en) * 2005-01-15 2006-07-20 Bayer Healthcare Ag Intravenous formulations of PDE inhibitors
DE102005009240A1 (en) * 2005-03-01 2006-09-07 Bayer Healthcare Ag Dosage forms with improved pharmacokinetic properties
WO2007016361A2 (en) 2005-07-29 2007-02-08 Concert Pharmaceuticals Inc. Novel pharmaceutical compounds
BRPI0616633A2 (en) * 2005-09-29 2011-06-28 Bayer Healthcare Ag pde inhibitors and combinations thereof for the treatment of urological disorders
DK1937276T3 (en) 2005-10-12 2013-02-11 Besins Healthcare Luxembourg IMPROVED TESTOSTERONGEL AND PROCEDURE TO USE THEREOF
US20070093493A1 (en) * 2005-10-12 2007-04-26 Lilly Icos Llc Treatment of benign prostatic hypertrophy and lower urinary tract symptoms
WO2008103470A2 (en) * 2007-02-21 2008-08-28 Trustees Of Columbia University In The City Of New York Oncogenic-ras-signal dependent lethal compounds
US20080216828A1 (en) 2007-03-09 2008-09-11 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
FR2916200A1 (en) * 2007-05-18 2008-11-21 Fourtillan Snc New 1,2,3,4,6,7,12,12a-octahydro-pyrazino(1',2':1,6)pyrido(3,4-b)indole compounds are 5-hydroxy tryptamine-2 receptor antagonist useful to treat e.g. depression, anxiety, Parkinson's disease, Alzheimer's disease and cancer
CA2689638A1 (en) * 2007-06-13 2008-12-18 Bayer Schering Pharma Aktiengesellschaft Pde inhibitors for the treatment of hearing impairment
EP2181997A1 (en) * 2008-10-30 2010-05-05 Chemo Ibérica, S.A. A process for the preparation of tadalafil
US9023890B2 (en) * 2009-12-02 2015-05-05 The Charlotte-Mecklenburg Hospital Authority Nitrate esters and their use for the treatment of muscle and muscle related diseases
US9452117B2 (en) 2011-06-01 2016-09-27 The Charlotte-Mecklenburg Hospital Authority Nitrate esters and their use for the treatment of muscle and muscle related diseases
CN104086546B (en) * 2014-07-14 2016-08-17 福建广生堂药业股份有限公司 Medicinal hydrochlorate of tadanafil and preparation method thereof
WO2017168174A1 (en) 2016-04-02 2017-10-05 N4 Pharma Uk Limited New pharmaceutical forms of sildenafil
CN106810554B (en) * 2017-01-14 2019-02-15 山东罗欣药业集团恒欣药业有限公司 A kind of preparation method of Tadalafei compound

Family Cites Families (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3644384A (en) * 1969-06-09 1972-02-22 Sterling Drug Inc Certain 2-(alpha-haloacetyl) - 1 2 3 4-tetrahydro - 9h - pyrido(3 4-b)indole-3-carboxylates and derivatives
US3717638A (en) * 1971-03-11 1973-02-20 Sterling Drug Inc 1,2,3,4,6,7,12,12A-OCTAHYDRO-2-PHENYLPYRAZINO[2',1':6,1]PYRIDO[3,4-b]INDOLES AND INTERMEDIATES THEREFOR
US3917599A (en) * 1973-03-30 1975-11-04 Council Scient Ind Res 2-Substituted-1,2,3,4,6,7,12,12A-octahydropyrazino(2{40 ,1{40 :6,1)pyrido(3,4-B)indoles
GB1454171A (en) * 1973-10-19 1976-10-27 Council Scient Ind Res Tetracyclic compounds
US4188390A (en) * 1977-11-05 1980-02-12 Pfizer Inc. Antihypertensive 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl) piperazin-1-yl or homopiperazin-1-yl]quinazolines
GR79603B (en) * 1982-07-24 1984-10-31 Pfizer
US4801587A (en) * 1987-03-02 1989-01-31 Gene Voss Impotence ointment
IT1217190B (en) * 1988-04-22 1990-03-14 Recordati Chem Pharm USEFUL COMPOUNDS FOR THE TREATMENT AND DIAGNOSIS OF HURRY DYSFUNCTIONS
EP0357122A3 (en) * 1988-08-29 1991-10-23 Duphar International Research B.V Use of beta-carbolines, their bio-isosteric benzofuran and benzothiophene analogues for the manufacture of a medicament having cytostatic properties
DE3830096A1 (en) * 1988-09-03 1990-03-15 Hoechst Ag PIPERAZINDIONE WITH PSYCHOTROPER EFFECT
FR2649613B1 (en) * 1989-07-11 1991-09-27 Virag Ronald VASO-ACTIVE MEDICINE
JPH0344324A (en) * 1989-07-13 1991-02-26 Kazuoki Tsuchiya Sexual function invigorator
US5270323A (en) * 1990-05-31 1993-12-14 Pfizer Inc. Method of treating impotence
DE69105040T2 (en) * 1990-05-31 1995-03-23 Pfizer Medicines for impotence.
GB9013750D0 (en) * 1990-06-20 1990-08-08 Pfizer Ltd Therapeutic agents
US5399581A (en) * 1990-12-26 1995-03-21 Laragh; John H. Method and compositions for treatment of sexual impotence
GB9114760D0 (en) * 1991-07-09 1991-08-28 Pfizer Ltd Therapeutic agents
DE4220264A1 (en) * 1992-06-20 1993-12-23 Cassella Ag Phenyl-1,2,5-oxadiazole-carbonamide-2-oxide
US5646181A (en) * 1992-07-02 1997-07-08 Research Foundation Of State University Of New York Method and compositions for treating impotence
GB9218322D0 (en) * 1992-08-28 1992-10-14 Pfizer Ltd Therapeutic agents
EP0611248B1 (en) * 1993-02-10 2000-03-22 B.M.R.A. Corporation B.V. Pharmaceutical composition for treating impotence containing an alpha-1-inhibitor and an alpha-2 inhibitor
US5698589A (en) * 1993-06-01 1997-12-16 International Medical Innovations, Inc. Water-based topical cream containing nitroglycerin and method of preparation and use thereof
GB9301192D0 (en) * 1993-06-09 1993-06-09 Trott Francis W Flower shaped mechanised table
US5565466A (en) * 1993-08-13 1996-10-15 Zonagen, Inc. Methods for modulating the human sexual response
CN1060042C (en) * 1993-10-27 2001-01-03 法玛西雅厄普约翰美国公司 Stabilized prostaglandin E 1
GB9514465D0 (en) * 1995-07-14 1995-09-13 Glaxo Lab Sa Chemical compounds
US6143746A (en) * 1994-01-21 2000-11-07 Icos Corporation Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use
GB9401090D0 (en) * 1994-01-21 1994-03-16 Glaxo Lab Sa Chemical compounds
DE69514794T2 (en) * 1994-04-22 2000-07-27 Pentech Pharmaceuticals Inc SUBLINGUAL DOSAGE FORMS CONTAINING APOMORPHIN FOR USE IN THE TREATMENT OF ERECTILE DYSFUNCTION
HU218280B (en) * 1994-04-26 2000-07-28 Cyclodextrin inclusion complexes containing sin-1a which are stable intheir solid state, process for their preparation and pharmaceutical compositions containing the comlexes
CA2215307A1 (en) * 1995-03-14 1996-09-19 Vivus, Incorporated Pharmaceutical compositions and kits for preventing erectile dysfunction
GB9511220D0 (en) * 1995-06-02 1995-07-26 Glaxo Group Ltd Solid dispersions
GB9514464D0 (en) * 1995-07-14 1995-09-13 Glaxo Lab Sa Medicaments
US5874437A (en) * 1996-11-01 1999-02-23 Nitromed, Inc. Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses
GB9700878D0 (en) * 1997-01-17 1997-03-05 Scherer Ltd R P Dosage forms and method for ameliorating male erectile dysfunction
WO2006104870A2 (en) * 2005-03-25 2006-10-05 Schering Corporation Methods of treating benign prostatic hyperplasia or lower urinary track symptoms by using pde 5 inhibitors
DE102005016981A1 (en) * 2005-04-13 2006-10-19 Bayer Healthcare Ag Combination therapy for benign prostatic hyperplasia
US20070093493A1 (en) * 2005-10-12 2007-04-26 Lilly Icos Llc Treatment of benign prostatic hypertrophy and lower urinary tract symptoms

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018188446A1 (en) * 2017-04-14 2018-10-18 中山大学 Evodiamine compounds, preparation method therefor and application thereof

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