JP2002529469A - Ｃｒｆレセプターアンタゴニストおよびそれに関する方法 - Google Patents
Ｃｒｆレセプターアンタゴニストおよびそれに関する方法Info
- Publication number
- JP2002529469A JP2002529469A JP2000581028A JP2000581028A JP2002529469A JP 2002529469 A JP2002529469 A JP 2002529469A JP 2000581028 A JP2000581028 A JP 2000581028A JP 2000581028 A JP2000581028 A JP 2000581028A JP 2002529469 A JP2002529469 A JP 2002529469A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- methyl
- ethyl
- compound according
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 25
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 title abstract description 40
- 229940044551 receptor antagonist Drugs 0.000 title abstract description 31
- 239000002464 receptor antagonist Substances 0.000 title abstract description 31
- 150000001875 compounds Chemical class 0.000 claims abstract description 89
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 208000035475 disorder Diseases 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 241001465754 Metazoa Species 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 206010010904 Convulsion Diseases 0.000 claims abstract description 6
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- -1 C3-6Alkenyl Chemical group 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 229930194542 Keto Natural products 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000000468 ketone group Chemical group 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 4
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
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- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
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- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 230000001506 immunosuppresive effect Effects 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 3
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
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- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 208000007101 Muscle Cramp Diseases 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
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- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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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- 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
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| 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 (2)
| Publication Number | Publication Date |
|---|---|
| JP2002529469A true JP2002529469A (ja) | 2002-09-10 |
| JP2002529469A5 JP2002529469A5 (OSRAM) | 2006-11-24 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2000581028A Pending JP2002529469A (ja) | 1998-11-12 | 1999-11-12 | Ｃｒｆレセプターアンタゴニストおよびそれに関する方法 |
Country Status (19)
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| US (3) | US6348466B1 (OSRAM) |
| EP (1) | EP1129096B1 (OSRAM) |
| JP (1) | JP2002529469A (OSRAM) |
| KR (1) | KR20010080402A (OSRAM) |
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| AT (1) | ATE240958T1 (OSRAM) |
| AU (1) | AU755997B2 (OSRAM) |
| BR (1) | BR9915129A (OSRAM) |
| CA (1) | CA2349904A1 (OSRAM) |
| DE (1) | DE69908173T2 (OSRAM) |
| DK (1) | DK1129096T3 (OSRAM) |
| ES (1) | ES2196898T3 (OSRAM) |
| HK (1) | HK1038925B (OSRAM) |
| IL (1) | IL143105A0 (OSRAM) |
| NO (1) | NO20012228D0 (OSRAM) |
| NZ (1) | NZ511267A (OSRAM) |
| PT (1) | PT1129096E (OSRAM) |
| TR (1) | TR200102178T2 (OSRAM) |
| WO (1) | WO2000027850A2 (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007515473A (ja) * | 2003-12-22 | 2007-06-14 | エスビー・ファルムコ・プエルト・リコ・インコーポレイテッド | Ｃｒｆ受容体アンタゴニストおよびそれらに関連する方法 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030016222A (ko) * | 2000-02-14 | 2003-02-26 | 니뽄 다바코 산교 가부시키가이샤 | 수술후 스트레스 예방ㆍ치료제 |
| WO2001083486A1 (en) * | 2000-05-01 | 2001-11-08 | Bristol-Myers Squibb Pharma Company | Tricyclic fused pyridine and pyrimidine derivatives as crf receptor antagonists |
| WO2001087889A1 (en) * | 2000-05-18 | 2001-11-22 | Neurocrine Biosciences, Inc. | Crf receptor antagonists and methods relating thereto |
| JP2003533526A (ja) * | 2000-05-18 | 2003-11-11 | ニューロクライン バイオサイエンシーズ， インコーポレイテッド | Ｃｒｆレセプターアンタゴニストおよびそれに関連する方法 |
| DE60126134T2 (de) * | 2000-11-03 | 2007-10-18 | Neurocrine Biosciences, Inc., San Diego | CRF-Rezeptorantagonisten und Verfahren, die damit in Beziehung stehen |
| JP2004518731A (ja) * | 2000-12-28 | 2004-06-24 | ニューロクライン バイオサイエンシーズ， インコーポレイテッド | 三環式ｃｒｆレセプターアンタゴニスト |
| ES2294047T3 (es) | 2000-12-28 | 2008-04-01 | Ono Pharmaceutical Co., Ltd. | Un compuesto de ciclopenta (d) pirazolo(1,5-a) pirimidina como antagonista del receptor de crf. |
| AU2002249474B2 (en) | 2001-04-30 | 2006-01-12 | Glaxo Group Limited | Crf receptor antagonists |
| 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 |
| ATE478873T1 (de) | 2003-06-25 | 2010-09-15 | Ono Pharmaceutical Co | Methansulfonsäuresalz einer pyrazolopyrimidinverbindung, kristall davon und verfahren zu deren herstellung |
| 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 |
| CN102453763A (zh) | 2004-06-03 | 2012-05-16 | 阿什洛米克斯控股有限公司 | 诊断应激的药物和方法 |
| 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 |
| 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 |
| WO2006026356A2 (en) | 2004-08-25 | 2006-03-09 | Ardea Biosciences, Inc. | S-TRIAZOLYL α-MERCAPTOACETANILDES AS INHIBITORS OF HIV REVERSE TRANSCRIPTASE |
| US8227601B2 (en) | 2005-05-05 | 2012-07-24 | Ardea Biosciences, Inc. | Diaryl-purines, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitor for treatment of HIV |
| US7595324B2 (en) | 2006-11-09 | 2009-09-29 | Ardea Biosciences, Inc. | Substituted thieno[3,2-D]pyrimidines as HIV inhibitors |
| BRPI0819847B1 (pt) | 2007-11-27 | 2022-01-11 | Ardea Biosciences, Inc | Compostos e composições |
| WO2009079412A2 (en) | 2007-12-14 | 2009-06-25 | Ardea Biosciences Inc. | Reverse transcriptase inhibitors |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04211086A (ja) * | 1990-02-21 | 1992-08-03 | American Cyanamid Co | ２，４，８−三置換−３Ｈ，６Ｈ−１，４，５ａ，８ａ−テトラアザアセナフチレン−３，５（４Ｈ）−ジオン類 |
| WO1994013677A1 (en) * | 1992-12-17 | 1994-06-23 | Pfizer Inc. | Pyrazolopyrimidines as crf antagonists |
| JPH07509726A (ja) * | 1992-12-17 | 1995-10-26 | フアイザー・インコーポレイテツド | Ｃｒｆアンタゴニストとしてのピロロピリミジン |
| JPH09507855A (ja) * | 1994-06-16 | 1997-08-12 | ファイザー・インコーポレーテッド | ピラゾロおよびピロロピリジン類 |
| WO1997044038A1 (en) * | 1996-05-23 | 1997-11-27 | Du Pont Pharmaceuticals Company | Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders |
| WO1998008847A1 (en) * | 1996-08-28 | 1998-03-05 | Pfizer Inc. | Substituted 6,5-hetero-bicyclic derivatives |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4605642A (en) | 1984-02-23 | 1986-08-12 | The Salk Institute For Biological Studies | CRF antagonists |
| 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. |
| CA2150703C (en) | 1992-12-17 | 2002-01-08 | Pfizer Limited | Substituted pyrazoles |
| TW336932B (en) | 1992-12-17 | 1998-07-21 | Pfizer | Amino-substituted pyrazoles |
| US5712303A (en) | 1992-12-17 | 1998-01-27 | Pfizer Inc. | Pyrazoles and pyrazolopyrimidines having CRF antagonistic activity |
| JP3398152B2 (ja) | 1993-10-12 | 2003-04-21 | ブリストル‐マイヤーズ・スクイブ・ファーマ・カンパニー | １ｎ−アルキル−ｎ−アリールピリミジンアミンおよびその誘導体 |
| TW574214B (en) | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
| JPH10506126A (ja) | 1995-05-12 | 1998-06-16 | ニューロゲン コーポレイション | 新規なデアザプリン誘導体；ｃｒｆ１特異性リガンドの新規なクラス |
| 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 |
| US6326368B1 (en) | 1996-03-27 | 2001-12-04 | Dupont Pharmaceuticals Company | Aryloxy- and arylthiosubstituted pyrimidines and triazines and derivatives thereof |
| US6107300A (en) | 1996-03-27 | 2000-08-22 | Dupont Pharmaceuticals | Arylamino fused pyrimidines |
| HU229024B1 (en) | 1996-07-24 | 2013-07-29 | Bristol Myers Squibb Pharma Co | Azolo-pyridimidines, pharmaceutical compositions containing the same and use thereof |
| NZ333727A (en) | 1996-08-06 | 2000-09-29 | Pfizer | Substituted pyrido- or pyrimido-containing 6,6- or 6,7-bicyclic arylsulfonylamino hydroxamic acid 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 |
| DE69710594T2 (de) | 1996-09-16 | 2002-08-29 | Du Pont Pharmaceuticals Co., Wilmington | Eine resorbierbare röntgenopake markierung enthaltendes chirurgisches implantat und verfahren zum verriegeln desselben in einem körper |
| 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 DK DK99961675T patent/DK1129096T3/da active
- 1999-11-12 AT AT99961675T patent/ATE240958T1/de not_active IP Right Cessation
- 1999-11-12 CN CNB998131725A patent/CN1178941C/zh not_active Expired - Fee Related
- 1999-11-12 JP JP2000581028A patent/JP2002529469A/ja active Pending
- 1999-11-12 NZ NZ511267A patent/NZ511267A/xx unknown
- 1999-11-12 BR BR9915129-4A patent/BR9915129A/pt not_active IP Right Cessation
- 1999-11-12 KR KR1020017005818A patent/KR20010080402A/ko not_active Ceased
- 1999-11-12 US US09/439,841 patent/US6348466B1/en not_active Expired - Fee Related
- 1999-11-12 DE DE69908173T patent/DE69908173T2/de not_active Expired - Lifetime
- 1999-11-12 HK HK02100689.4A patent/HK1038925B/en not_active IP Right Cessation
- 1999-11-12 AU AU18199/00A patent/AU755997B2/en not_active Ceased
- 1999-11-12 PT PT99961675T patent/PT1129096E/pt unknown
- 1999-11-12 ES ES99961675T patent/ES2196898T3/es not_active Expired - Lifetime
- 1999-11-12 EP EP99961675A patent/EP1129096B1/en not_active Expired - Lifetime
- 1999-11-12 WO PCT/US1999/026984 patent/WO2000027850A2/en not_active Ceased
- 1999-11-12 CA CA002349904A patent/CA2349904A1/en not_active Abandoned
- 1999-11-12 TR TR2001/02178T patent/TR200102178T2/xx unknown
- 1999-11-12 IL IL14310599A patent/IL143105A0/xx unknown
-
2001
- 2001-05-04 NO NO20012228A patent/NO20012228D0/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
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04211086A (ja) * | 1990-02-21 | 1992-08-03 | American Cyanamid Co | ２，４，８−三置換−３Ｈ，６Ｈ−１，４，５ａ，８ａ−テトラアザアセナフチレン−３，５（４Ｈ）−ジオン類 |
| WO1994013677A1 (en) * | 1992-12-17 | 1994-06-23 | Pfizer Inc. | Pyrazolopyrimidines as crf antagonists |
| JPH07509726A (ja) * | 1992-12-17 | 1995-10-26 | フアイザー・インコーポレイテツド | Ｃｒｆアンタゴニストとしてのピロロピリミジン |
| JPH09507855A (ja) * | 1994-06-16 | 1997-08-12 | ファイザー・インコーポレーテッド | ピラゾロおよびピロロピリジン類 |
| WO1997044038A1 (en) * | 1996-05-23 | 1997-11-27 | Du Pont Pharmaceuticals Company | Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders |
| WO1998008847A1 (en) * | 1996-08-28 | 1998-03-05 | Pfizer Inc. | Substituted 6,5-hetero-bicyclic derivatives |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007515473A (ja) * | 2003-12-22 | 2007-06-14 | エスビー・ファルムコ・プエルト・リコ・インコーポレイテッド | Ｃｒｆ受容体アンタゴニストおよびそれらに関連する方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000027850A2 (en) | 2000-05-18 |
| EP1129096B1 (en) | 2003-05-21 |
| DE69908173T2 (de) | 2004-08-19 |
| AU755997B2 (en) | 2003-01-02 |
| HK1038925A1 (en) | 2002-04-04 |
| DE69908173D1 (de) | 2003-06-26 |
| US6348466B1 (en) | 2002-02-19 |
| IL143105A0 (en) | 2002-04-21 |
| ES2196898T3 (es) | 2003-12-16 |
| NO20012228L (no) | 2001-05-04 |
| CA2349904A1 (en) | 2000-05-18 |
| PT1129096E (pt) | 2003-09-30 |
| TR200102178T2 (tr) | 2002-01-21 |
| BR9915129A (pt) | 2001-08-07 |
| NZ511267A (en) | 2002-12-20 |
| EP1129096A2 (en) | 2001-09-05 |
| CN1178941C (zh) | 2004-12-08 |
| WO2000027850A3 (en) | 2000-08-03 |
| ATE240958T1 (de) | 2003-06-15 |
| KR20010080402A (ko) | 2001-08-22 |
| NO20012228D0 (no) | 2001-05-04 |
| AU1819900A (en) | 2000-05-29 |
| US20040229879A1 (en) | 2004-11-18 |
| US20020143008A1 (en) | 2002-10-03 |
| US6723721B2 (en) | 2004-04-20 |
| HK1038925B (en) | 2003-12-05 |
| DK1129096T3 (da) | 2003-09-15 |
| CN1326458A (zh) | 2001-12-12 |
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