ATE211139T1 - Tetrahydroimidazopyridoindoldione als cgmp spezifische pde hemmer - Google Patents

Tetrahydroimidazopyridoindoldione als cgmp spezifische pde hemmer

Info

Publication number
ATE211139T1
ATE211139T1 AT96925709T AT96925709T ATE211139T1 AT E211139 T1 ATE211139 T1 AT E211139T1 AT 96925709 T AT96925709 T AT 96925709T AT 96925709 T AT96925709 T AT 96925709T AT E211139 T1 ATE211139 T1 AT E211139T1
Authority
AT
Austria
Prior art keywords
tetrahydroimidazopyridoindoldione
pde inhibitors
specific pde
cgmp specific
cgmp
Prior art date
Application number
AT96925709T
Other languages
English (en)
Inventor
Alain Claude-Marie Daugan
Richard Frederic Labaudiniere
Original Assignee
Icos Corp
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 Icos Corp filed Critical Icos Corp
Application granted granted Critical
Publication of ATE211139T1 publication Critical patent/ATE211139T1/de

Links

Classifications

    • 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
    • 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
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • A61P11/06—Antiasthmatics
    • 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
    • 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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • A61P9/10—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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Reproductive Health (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Gynecology & Obstetrics (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
AT96925709T 1995-07-14 1996-07-11 Tetrahydroimidazopyridoindoldione als cgmp spezifische pde hemmer ATE211139T1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9514473.9A GB9514473D0 (en) 1995-07-14 1995-07-14 Chemical compounds
PCT/EP1996/003023 WO1996032003A2 (en) 1995-07-14 1996-07-11 Tetrahydroimidazopyridoindolediones and their use as medicaments

Publications (1)

Publication Number Publication Date
ATE211139T1 true ATE211139T1 (de) 2002-01-15

Family

ID=10777704

Family Applications (1)

Application Number Title Priority Date Filing Date
AT96925709T ATE211139T1 (de) 1995-07-14 1996-07-11 Tetrahydroimidazopyridoindoldione als cgmp spezifische pde hemmer

Country Status (13)

Country Link
US (3) US6001847A (de)
EP (1) EP0859778B1 (de)
JP (1) JP4012246B2 (de)
CN (1) CN1095841C (de)
AT (1) ATE211139T1 (de)
AU (1) AU702548B2 (de)
BR (1) BR9609503A (de)
CA (1) CA2226759A1 (de)
DE (1) DE69618231T2 (de)
ES (1) ES2170252T3 (de)
GB (1) GB9514473D0 (de)
MX (1) MX9800415A (de)
WO (1) WO1996032003A2 (de)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU756136B2 (en) 1997-06-23 2003-01-02 Queen's University At Kingston Microdose therapy
US6403597B1 (en) 1997-10-28 2002-06-11 Vivus, Inc. Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation
US6548490B1 (en) * 1997-10-28 2003-04-15 Vivus, Inc. Transmucosal administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction
AU1025899A (en) * 1998-09-16 2000-04-03 Icos Corporation Carboline derivatives as cgmp phosphodiesterase inhibitors
ES2187234A1 (es) * 1999-04-30 2003-05-16 Lilly Icos Llc Forma de dosificacion oral para tratar la disfuncion sexual.
US6451807B1 (en) 1999-04-30 2002-09-17 Lilly Icos, Llc. Methods of treating sexual dysfunction in an individual suffering from a retinal disease, class 1 congestive heart failure, or myocardial infarction using a PDE5 inhibitor
US20010036959A1 (en) * 2000-04-03 2001-11-01 Gabel Rolf Dieter Carvedilol-hydrophilic solutions
US20020006926A1 (en) 2000-04-19 2002-01-17 Roylance H. H. Use of cyclic GMP-specific phosphodiesterase inhibitors for treatment of parkinson's disease
MXPA02012470A (es) 2000-06-23 2004-01-26 Lilly Icos Llc Inhibidores de fosfodiesterasa especificos para gmp ciclico.
CA2423308A1 (en) 2000-10-02 2002-04-11 Lilly Icos Llc Condensed pyridoindole derivatives
DE60121461T2 (de) * 2000-10-03 2007-02-08 Lilly Icos Llc, Wilmington Kondensierte pyridoindolderivate
NZ527585A (en) * 2001-02-15 2005-04-29 Tanabe Seiyaku Co Tablets quickly disintegrated in oral cavity
DE10118306A1 (de) 2001-04-12 2002-10-17 Bayer Ag Imidazotriazinonhaltige Zusammensetzungen zur nasalen Applikation
EP1383765B1 (de) 2001-04-25 2006-12-13 Lilly Icos LLC Carbolin Derivate als Hemmstoffe von Phospphodiesterase 5 (PDE5) zur Behandlung kardiovaskulärer Erkrankungen und der erektilen Dysfunktion
EP1401835A1 (de) * 2001-06-05 2004-03-31 Lilly Icos LLC Carbolinderivate als pde 5 inhibitoren
DE60235198D1 (de) * 2001-12-20 2010-03-11 Merck Serono Sa Coinsins Pyrrolidin-derivatie als prostaglandin-modulatoren
MY140561A (en) * 2002-02-20 2009-12-31 Nycomed Gmbh Dosage form containing pde 4 inhibitor as active ingredient
US7276529B2 (en) * 2002-03-20 2007-10-02 Celgene Corporation Methods of the treatment or prevention of exercise-induced asthma using (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione
US7208516B2 (en) * 2002-03-20 2007-04-24 Celgene Corporation Methods of the treatment of psoriatic arthritis using (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione
US6962940B2 (en) 2002-03-20 2005-11-08 Celgene Corporation (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof
US7893101B2 (en) 2002-03-20 2011-02-22 Celgene Corporation Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof
ES2211295B1 (es) * 2002-07-19 2005-12-01 Consejo Sup. De Investig. Cientificas Tetrahidro-beta-carbolinas fenolicas como antioxidantes.
NZ537784A (en) * 2002-07-31 2008-01-31 Lilly Icos Llc Modified Pictet-Spengler reaction and products prepared therefrom
US20050048573A1 (en) * 2003-02-03 2005-03-03 Plexxikon, Inc. PDE5A crystal structure and uses
ES2335498T3 (es) 2003-03-10 2010-03-29 Nycomed Gmbh Nuevo proceso para la preparacion de reflumilast.
JP2007501866A (ja) * 2003-06-13 2007-02-01 マイクロバイア インコーポレイテッド 胃腸疾患の治療のための方法および組成物
DE10348022A1 (de) * 2003-10-15 2005-05-25 Imtm Gmbh Neue Dipeptidylpeptidase IV-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen
US8076353B2 (en) 2004-03-15 2011-12-13 Ptc Therapeutics, Inc. Inhibition of VEGF translation
US8940896B2 (en) 2004-03-15 2015-01-27 Ptc Therapeutics, Inc. Tetra-cyclic carboline derivatives useful in the inhibition of angiogenesis
US8076352B2 (en) 2004-03-15 2011-12-13 Ptc Therapeutics, Inc. Administration of carboline derivatives useful in the treatment of cancer and other diseases
US7767689B2 (en) 2004-03-15 2010-08-03 Ptc Therapeutics, Inc. Carboline derivatives useful in the treatment of cancer
UA92317C2 (ru) 2004-03-15 2010-10-25 Пи-Ти-Си ТЕРАПЬЮТИКС, ИНК. Производные карболина, пригодные для ингибирования развития кровеносных сосудов
ATE486878T1 (de) 2004-08-18 2010-11-15 4Sc Ag Benzothienopyridine zur verwendung als inhibitoren von eg5-kinesin
US8663694B2 (en) * 2005-03-16 2014-03-04 Takeda Gmbh Taste masked dosage form containing roflumilast
US20070155791A1 (en) * 2005-12-29 2007-07-05 Zeldis Jerome B Methods for treating cutaneous lupus using aminoisoindoline compounds
KR101415354B1 (ko) 2006-02-22 2014-07-04 4에스체 악티엔게젤샤프트 Ｅｇ5 키네신 조절제로서의 인돌로피리딘
WO2007113243A2 (en) * 2006-03-31 2007-10-11 Investigación Y Clínica Andrológicas S.L. Use of pde 5 inhibitors for the treatment of overactive bladder
FR2912405A1 (fr) * 2007-02-08 2008-08-15 Fourtillan Snc Derives des imidazo[1',5':1,6]pyrido[3,4-b]indoles et leur utilisation en therapeutique
WO2009024190A1 (en) * 2007-08-22 2009-02-26 4Sc Ag Indolopyridines as inhibitors of the kinesin spindle protein (eg5 )
EP2098524A1 (de) * 2008-03-05 2009-09-09 4Sc Ag Verfahren zur Herstellung enantiomerenreiner Indolopyrinidine
JP2011515469A (ja) * 2008-03-24 2011-05-19 セルジーン コーポレイション シクロプロピル−ｎ−｛２−［（１ｓ）−１−（３−エトキシ−４−メトキシフェニル）−２−（メチルスルホニル）エチル］−３−オキソイソインドリン−４−イル｝カルボキサミドを使用した乾癬又は乾癬性関節炎の治療
US9926318B2 (en) * 2013-11-22 2018-03-27 Pharmakea, Inc. Tetracyclic autotaxin inhibitors
EP3071561B1 (de) 2013-11-22 2021-03-24 Sabre Therapeutics LLC Autotaxin-inhibitorverbindungen
US20160317542A1 (en) 2013-12-09 2016-11-03 Respira Therapeutics, Inc. Pde5 inhibitor powder formulations and methods relating thereto
MX2016014384A (es) 2014-06-23 2017-01-20 Celgene Corp Apremilast para el tratamiento de una enfermedad del higado o una anormalidad en la funcion del higado.
CA2986759C (en) 2015-05-27 2025-06-17 Sabre Therapeutics Llc AUTOTAXIN INHIBITORS AND THEIR USES
WO2017168174A1 (en) 2016-04-02 2017-10-05 N4 Pharma Uk Limited New pharmaceutical forms of sildenafil

Family Cites Families (22)

* 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 (de) * 1982-07-24 1984-10-31 Pfizer
US4801587A (en) * 1987-03-02 1989-01-31 Gene Voss Impotence ointment
IT1217190B (it) * 1988-04-22 1990-03-14 Recordati Chem Pharm Composti utili per il trattamento e diagnosi di disfunzioni frettili
EP0357122A3 (de) * 1988-08-29 1991-10-23 Duphar International Research B.V Verwendung von Beta-Carbolinen und deren bio-isosterischen Benzofuran- und Benzothiophenanalogen zur Herstellung eines Arzneimittels mit cytostatischer Wirkung
DE3830096A1 (de) * 1988-09-03 1990-03-15 Hoechst Ag Piperazindione mit psychotroper wirkung
FR2649613B1 (fr) * 1989-07-11 1991-09-27 Virag Ronald Medicament vaso-actif
JPH0344324A (ja) * 1989-07-13 1991-02-26 Kazuoki Tsuchiya 性機能賦活剤
US5270323A (en) * 1990-05-31 1993-12-14 Pfizer Inc. Method of treating impotence
EP0459666B1 (de) * 1990-05-31 1994-11-09 Pfizer Inc. Arzneimittel gegen Impotenz
GB9013750D0 (en) * 1990-06-20 1990-08-08 Pfizer Ltd Therapeutic agents
GB9114760D0 (en) * 1991-07-09 1991-08-28 Pfizer Ltd Therapeutic agents
GB9218322D0 (en) * 1992-08-28 1992-10-14 Pfizer Ltd Therapeutic agents
GB9311920D0 (en) * 1993-06-09 1993-07-28 Pfizer Ltd Therapeutic agents
GB9514465D0 (en) * 1995-07-14 1995-09-13 Glaxo Lab Sa Chemical compounds
GB9401090D0 (en) * 1994-01-21 1994-03-16 Glaxo Lab Sa Chemical compounds
WO1995028930A1 (en) * 1994-04-22 1995-11-02 Pentech Pharmaceuticals, Inc. Dosage forms and method for ameliorating male erectile dysfunction
US5874437A (en) * 1996-11-01 1999-02-23 Nitromed, Inc. Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses

Also Published As

Publication number Publication date
CN1095841C (zh) 2002-12-11
JPH11509517A (ja) 1999-08-24
ES2170252T3 (es) 2002-08-01
DE69618231D1 (de) 2002-01-31
US6001847A (en) 1999-12-14
EP0859778B1 (de) 2001-12-19
EP0859778A2 (de) 1998-08-26
US6218400B1 (en) 2001-04-17
US6143757A (en) 2000-11-07
DE69618231T2 (de) 2002-08-22
AU702548B2 (en) 1999-02-25
GB9514473D0 (en) 1995-09-13
WO1996032003A3 (en) 1997-01-03
JP4012246B2 (ja) 2007-11-21
CN1195350A (zh) 1998-10-07
CA2226759A1 (en) 1996-10-17
BR9609503A (pt) 2000-03-08
AU6613896A (en) 1996-10-30
MX9800415A (es) 1998-04-30
WO1996032003A2 (en) 1996-10-17

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