KR20010080402A - Ｃｒｆ 수용체 길항제 및 그와 관련된 방법 - Google Patents
Ｃｒｆ 수용체 길항제 및 그와 관련된 방법 Download PDFInfo
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- KR20010080402A KR20010080402A KR1020017005818A KR20017005818A KR20010080402A KR 20010080402 A KR20010080402 A KR 20010080402A KR 1020017005818 A KR1020017005818 A KR 1020017005818A KR 20017005818 A KR20017005818 A KR 20017005818A KR 20010080402 A KR20010080402 A KR 20010080402A
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- alkyl
- methyl
- ethyl
- compound according
- phenyl
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Classifications
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- 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
- C07D471/16—Peri-condensed systems
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- 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]
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- A—HUMAN NECESSITIES
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- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Addiction (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19095898A | 1998-11-12 | 1998-11-12 | |
| US09/190,958 | 1998-11-12 | ||
| US40074499A | 1999-09-21 | 1999-09-21 | |
| US09/400,744 | 1999-09-21 | ||
| PCT/US1999/026984 WO2000027850A2 (en) | 1998-11-12 | 1999-11-12 | Crf receptor antagonists and methods relating thereto |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20010080402A true KR20010080402A (ko) | 2001-08-22 |
Family
ID=26886600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020017005818A Ceased KR20010080402A (ko) | 1998-11-12 | 1999-11-12 | Ｃｒｆ 수용체 길항제 및 그와 관련된 방법 |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US6348466B1 (https=) |
| EP (1) | EP1129096B1 (https=) |
| JP (1) | JP2002529469A (https=) |
| KR (1) | KR20010080402A (https=) |
| CN (1) | CN1178941C (https=) |
| AT (1) | ATE240958T1 (https=) |
| AU (1) | AU755997B2 (https=) |
| BR (1) | BR9915129A (https=) |
| CA (1) | CA2349904A1 (https=) |
| DE (1) | DE69908173T2 (https=) |
| DK (1) | DK1129096T3 (https=) |
| ES (1) | ES2196898T3 (https=) |
| HK (1) | HK1038925B (https=) |
| IL (1) | IL143105A0 (https=) |
| NO (1) | NO20012228L (https=) |
| NZ (1) | NZ511267A (https=) |
| PT (1) | PT1129096E (https=) |
| TR (1) | TR200102178T2 (https=) |
| WO (1) | WO2000027850A2 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2398956A1 (en) * | 2000-02-14 | 2001-08-16 | Japan Tobacco Inc. | A pharmaceutical composition for prophylaxis or therapy of a postoperative stress |
| CA2407597A1 (en) * | 2000-05-01 | 2001-11-08 | Dupont Pharmaceuticals Company | Tricyclic fused pyridine and pyrimidine derivatives as crf receptor antagonists |
| AU2001263329A1 (en) * | 2000-05-18 | 2001-11-26 | Neurocrine Biosciences, Inc. | Crf receptor antagonists and methods relating thereto |
| ES2207614T3 (es) * | 2000-05-18 | 2004-06-01 | Neurocrine Biosciences, Inc. | Antagonistas del receptor de crf y metodos relacionados con estos. |
| KR20030060927A (ko) * | 2000-11-03 | 2003-07-16 | 뉴로크린 바이오사이언시즈 인코퍼레이티드 | Ｃｒｆ 수용체 길항제 및 이와 관련된 방법 |
| WO2002064592A1 (en) * | 2000-12-28 | 2002-08-22 | Neurocrine Biosciences, Inc. | Tricyclic crf receptor antagonists |
| DE60130924T2 (de) | 2000-12-28 | 2008-07-17 | Ono Pharmaceutical Co. Ltd. | Cyclopentaädüpyrazoloä1,5-aüpyrimidin-verbindung als crf-rezeptor antagonist |
| ES2255610T3 (es) | 2001-04-30 | 2006-07-01 | Glaxo Group Limited | Antagonistas de los receptores de crf. |
| GB0117395D0 (en) * | 2001-07-17 | 2001-09-05 | Glaxo Group Ltd | Chemical compounds |
| US7273871B2 (en) | 2001-07-17 | 2007-09-25 | Sb Pharmco Puerto Rico Inc. | Phenyl-5,6,6A,7,8,9-hexahydro-4H-1,4,9-triaza-phenalene derivatives as CRF antagonists |
| CN100422186C (zh) | 2003-06-25 | 2008-10-01 | 小野药品工业株式会社 | 吡唑并嘧啶化合物的甲磺酸盐、其结晶及其制备方法 |
| US20060024661A1 (en) * | 2003-07-30 | 2006-02-02 | The Regents Of The University Of California | Modulation of CRF potentiation of NMDA receptor currents via CRF receptor 2 |
| ATE388150T1 (de) * | 2003-12-22 | 2008-03-15 | Sb Pharmco Inc | Crf-rezeptorantagonisten und diese betreffende verfahren |
| NZ551782A (en) | 2004-06-03 | 2010-03-26 | Athlomics Pty Ltd | Agents and methods for diagnosing stress |
| CA2576435A1 (en) * | 2004-08-09 | 2006-03-23 | Research Development Foundation | Determination of the 3d-structure of an extracellular domain of a b1 g-protein coupled receptor by nmr analysis |
| ES2374773T3 (es) | 2004-08-25 | 2012-02-21 | Ardea Biosciences, Inc. | S-triazolil alfa-mercaptoacetanilidas como inhibidores de la transcriptasa inversa del vih. |
| WO2007050087A1 (en) | 2004-08-25 | 2007-05-03 | Ardea Biosciences, Inc. | N[S(4-aryl-triazol-3-yl)α -mercaptoacetyl]-p-amino benozoic acids AS HIV REVERSE TRANSCRIPTASE INHIBITORS |
| WO2006122003A2 (en) | 2005-05-05 | 2006-11-16 | Ardea Biosciences, Inc. | Diaryl-purine, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of hiv |
| EP2132211A4 (en) | 2006-11-09 | 2011-12-07 | Ardea Biosciences Inc | 4-CYANPHENYLAMINO-SUBSTITUTED BICYCLIC AND HETEROCYCLIC COMPOUNDS AS AN HIV HEMMER |
| JP5099794B2 (ja) | 2007-11-27 | 2012-12-19 | アルデア バイオサイエンシーズ インク． | 新規化合物、組成物、及び使用方法 |
| ES2389752T3 (es) | 2007-12-14 | 2012-10-31 | Ardea Biosciences, Inc. | Inhibidores de la transcriptasa inversa |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4605642A (en) | 1984-02-23 | 1986-08-12 | The Salk Institute For Biological Studies | CRF antagonists |
| US5013737A (en) * | 1988-02-22 | 1991-05-07 | American Cyanamid Company | 2,4,8-Trisubstituted-3H,6H-1,4,5A,8A-tetraazaacenaphtylene-3,5-(4H)-diones and 2,4-8-trisubstituted-4,5-dihydro-5-thioxo-3H,6H-1,4,5A,8A-tetrazaacenaphthylen-3-ones |
| US4904658A (en) | 1988-04-15 | 1990-02-27 | American Cyanamid Company | Substituted-6H,8H-pyrimido-[1,2,3-cd]purine-8,10-(9H)-diones and substituted-6H,10H-pyrimido[1,2-cd]purin-10-ones |
| US5063245A (en) | 1990-03-28 | 1991-11-05 | Nova Pharmaceutical Corporation | Corticotropin-releasing factor antagonism compounds |
| FR2692893B1 (fr) | 1992-06-24 | 1994-09-02 | Sanofi Elf | Dérivés alkylamino ramifiés du thiazole, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent. |
| TW336932B (en) | 1992-12-17 | 1998-07-21 | Pfizer | Amino-substituted pyrazoles |
| DK0674624T3 (da) | 1992-12-17 | 1999-09-13 | Pfizer | Pyrazoler med CRF-antagonistisk aktivitet |
| ATE177101T1 (de) * | 1992-12-17 | 1999-03-15 | Pfizer | Pyrrolopyrimidine als crf antagonisten |
| TW370529B (en) | 1992-12-17 | 1999-09-21 | Pfizer | Pyrazolopyrimidines |
| KR100190730B1 (ko) | 1992-12-17 | 1999-06-01 | 디. 제이. 우드, 스피겔 알렌 제이 | 부신피질 호르몬 유리인자(crf) 길항물질로서 치환된 피라졸 |
| RU2153494C2 (ru) | 1993-10-12 | 2000-07-27 | Дзе Дюпон Мерк Фармасьютикал Компани | 1-n-алкил-n-арилпиримидинамины, способ лечения заболеваний, фармацевтическая композиция |
| TW530047B (en) | 1994-06-08 | 2003-05-01 | Pfizer | Corticotropin releasing factor antagonists |
| WO1995034563A1 (en) | 1994-06-16 | 1995-12-21 | Pfizer Inc. | Pyrazolo and pyrrolopyridines |
| US6020492A (en) | 1995-05-12 | 2000-02-01 | Neurogen Corporation | Deazapurine derivatives; a new class of CRF1 specific ligands |
| FR2735777B1 (fr) | 1995-06-21 | 1997-09-12 | Sanofi Sa | Derives de 4-phenylaminothiazole, leur procede de preparation et les compositions pharmaceutiques les contenant |
| EP0901476A4 (en) | 1996-03-26 | 2001-08-16 | Du Pont Pharm Co | PYRIDINES AND PYRIMIDINES FUSION ARYLOXY AND ARYLTHIO AND DERIVATIVES THEREOF |
| US6107300A (en) | 1996-03-27 | 2000-08-22 | Dupont Pharmaceuticals | Arylamino fused pyrimidines |
| US6326368B1 (en) | 1996-03-27 | 2001-12-04 | Dupont Pharmaceuticals Company | Aryloxy- and arylthiosubstituted pyrimidines and triazines and derivatives thereof |
| ZA973884B (en) * | 1996-05-23 | 1998-11-06 | Du Pont Merck Pharma | Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders |
| HU228962B1 (en) | 1996-07-24 | 2013-07-29 | Bristol Myers Squibb Pharma Co | Azolo triazines, pharmaceutical compositions containing them and use of the compounds |
| US6492520B1 (en) | 1996-08-06 | 2002-12-10 | Pfizer Inc | Substituted pyrido-or pyrimido-containing 6,6- or 6,7-bicyclic derivatives |
| TW477787B (en) | 1996-08-27 | 2002-03-01 | Pfizer | Pyrido six-membered nitrogen-containing cyclic ring derivatives having corticotropin releasing factor antagonist activity and pharmaceutical composition containing same |
| IL127566A0 (en) * | 1996-08-28 | 1999-10-28 | Pfizer | Substituted 6,5-hetero- bicyclic derivatives |
| US6159980A (en) | 1996-09-16 | 2000-12-12 | Dupont Pharmaceuticals Company | Pyrazinones and triazinones and their derivatives thereof |
| FR2754258B1 (fr) | 1996-10-08 | 1998-12-31 | Sanofi Sa | Derives d'aminothiazole, leur procede de preparation et les compositions pharmaceutiques les contenant |
| US5760225A (en) | 1996-11-15 | 1998-06-02 | Neurogen Corporation | Certain pyrazole derivatives as corticotropin-releasing factor receptor CRF1 specific ligands |
| US5723608A (en) | 1996-12-31 | 1998-03-03 | Neurogen Corporation | 3-aryl substituted pyrazolo 4,3-d!pyrimidine derivatives; corticotropin-releasing factor receptor (CRF1) specific ligands |
-
1999
- 1999-11-12 EP EP99961675A patent/EP1129096B1/en not_active Expired - Lifetime
- 1999-11-12 KR KR1020017005818A patent/KR20010080402A/ko not_active Ceased
- 1999-11-12 CA CA002349904A patent/CA2349904A1/en not_active Abandoned
- 1999-11-12 NZ NZ511267A patent/NZ511267A/xx unknown
- 1999-11-12 AU AU18199/00A patent/AU755997B2/en not_active Ceased
- 1999-11-12 AT AT99961675T patent/ATE240958T1/de not_active IP Right Cessation
- 1999-11-12 JP JP2000581028A patent/JP2002529469A/ja active Pending
- 1999-11-12 US US09/439,841 patent/US6348466B1/en not_active Expired - Fee Related
- 1999-11-12 ES ES99961675T patent/ES2196898T3/es not_active Expired - Lifetime
- 1999-11-12 BR BR9915129-4A patent/BR9915129A/pt not_active IP Right Cessation
- 1999-11-12 PT PT99961675T patent/PT1129096E/pt unknown
- 1999-11-12 DE DE69908173T patent/DE69908173T2/de not_active Expired - Lifetime
- 1999-11-12 TR TR2001/02178T patent/TR200102178T2/xx unknown
- 1999-11-12 CN CNB998131725A patent/CN1178941C/zh not_active Expired - Fee Related
- 1999-11-12 IL IL14310599A patent/IL143105A0/xx unknown
- 1999-11-12 DK DK99961675T patent/DK1129096T3/da active
- 1999-11-12 HK HK02100689.4A patent/HK1038925B/en not_active IP Right Cessation
- 1999-11-12 WO PCT/US1999/026984 patent/WO2000027850A2/en not_active Ceased
-
2001
- 2001-05-04 NO NO20012228A patent/NO20012228L/no not_active Application Discontinuation
- 2001-12-20 US US10/027,789 patent/US6723721B2/en not_active Expired - Lifetime
-
2004
- 2004-02-23 US US10/785,386 patent/US20040229879A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000027850A2 (en) | 2000-05-18 |
| AU755997B2 (en) | 2003-01-02 |
| ES2196898T3 (es) | 2003-12-16 |
| JP2002529469A (ja) | 2002-09-10 |
| HK1038925B (en) | 2003-12-05 |
| DE69908173D1 (de) | 2003-06-26 |
| US6723721B2 (en) | 2004-04-20 |
| ATE240958T1 (de) | 2003-06-15 |
| EP1129096A2 (en) | 2001-09-05 |
| HK1038925A1 (en) | 2002-04-04 |
| DE69908173T2 (de) | 2004-08-19 |
| DK1129096T3 (da) | 2003-09-15 |
| NO20012228D0 (no) | 2001-05-04 |
| EP1129096B1 (en) | 2003-05-21 |
| NZ511267A (en) | 2002-12-20 |
| CN1178941C (zh) | 2004-12-08 |
| IL143105A0 (en) | 2002-04-21 |
| WO2000027850A3 (en) | 2000-08-03 |
| AU1819900A (en) | 2000-05-29 |
| CA2349904A1 (en) | 2000-05-18 |
| PT1129096E (pt) | 2003-09-30 |
| BR9915129A (pt) | 2001-08-07 |
| US20040229879A1 (en) | 2004-11-18 |
| CN1326458A (zh) | 2001-12-12 |
| US6348466B1 (en) | 2002-02-19 |
| TR200102178T2 (tr) | 2002-01-21 |
| NO20012228L (no) | 2001-05-04 |
| US20020143008A1 (en) | 2002-10-03 |
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