NO313636B1 - Substituerte 6,5-hetero-bicykliske derivater, anvendelse derav samt farmasöytiske preparater - Google Patents
Substituerte 6,5-hetero-bicykliske derivater, anvendelse derav samt farmasöytiske preparater Download PDFInfo
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- NO313636B1 NO313636B1 NO19990927A NO990927A NO313636B1 NO 313636 B1 NO313636 B1 NO 313636B1 NO 19990927 A NO19990927 A NO 19990927A NO 990927 A NO990927 A NO 990927A NO 313636 B1 NO313636 B1 NO 313636B1
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US2503996P | 1996-08-28 | 1996-08-28 | |
PCT/IB1997/000922 WO1998008847A1 (en) | 1996-08-28 | 1997-07-25 | Substituted 6,5-hetero-bicyclic derivatives |
Publications (3)
Publication Number | Publication Date |
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NO990927L NO990927L (no) | 1999-02-26 |
NO990927D0 NO990927D0 (no) | 1999-02-26 |
NO313636B1 true NO313636B1 (no) | 2002-11-04 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO19990927A NO313636B1 (no) | 1996-08-28 | 1999-02-26 | Substituerte 6,5-hetero-bicykliske derivater, anvendelse derav samt farmasöytiske preparater |
Country Status (36)
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EP (1) | EP0923582B1 (de) |
JP (2) | JP3621706B2 (de) |
KR (1) | KR20000035934A (de) |
CN (1) | CN1227554A (de) |
AP (1) | AP762A (de) |
AR (1) | AR015103A1 (de) |
AT (1) | ATE340176T1 (de) |
AU (1) | AU735401B2 (de) |
BG (1) | BG103189A (de) |
BR (1) | BR9711970A (de) |
CA (1) | CA2263566C (de) |
CO (1) | CO4600634A1 (de) |
CZ (1) | CZ68199A3 (de) |
DE (1) | DE69736711T2 (de) |
DZ (1) | DZ2300A1 (de) |
EA (1) | EA002769B1 (de) |
ES (1) | ES2273369T3 (de) |
GT (1) | GT199700095A (de) |
HR (1) | HRP970454B1 (de) |
HU (1) | HUP9903965A3 (de) |
ID (1) | ID18249A (de) |
IL (1) | IL127566A0 (de) |
IS (1) | IS4963A (de) |
MA (1) | MA26438A1 (de) |
NO (1) | NO313636B1 (de) |
NZ (1) | NZ333302A (de) |
OA (1) | OA10977A (de) |
PA (1) | PA8436201A1 (de) |
PE (1) | PE108898A1 (de) |
PL (1) | PL332040A1 (de) |
SK (1) | SK23399A3 (de) |
TN (1) | TNSN97145A1 (de) |
TR (1) | TR199900389T2 (de) |
TW (1) | TW575573B (de) |
WO (1) | WO1998008847A1 (de) |
ZA (1) | ZA977687B (de) |
Families Citing this family (147)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2194756A1 (en) | 1995-05-12 | 1996-11-14 | Jun Yuan | Novel deazapurine derivatives; a new class of crf1 specific ligands |
US7094782B1 (en) | 1996-07-24 | 2006-08-22 | Bristol-Myers Squibb Company | Azolo triazines and pyrimidines |
US6060478A (en) * | 1996-07-24 | 2000-05-09 | Dupont Pharmaceuticals | Azolo triazines and pyrimidines |
US6313124B1 (en) | 1997-07-23 | 2001-11-06 | Dupont Pharmaceuticals Company | Tetrazine bicyclic compounds |
US6191131B1 (en) | 1997-07-23 | 2001-02-20 | Dupont Pharmaceuticals Company | Azolo triazines and pyrimidines |
US6124289A (en) * | 1996-07-24 | 2000-09-26 | Dupont Pharmaceuticals Co. | Azolo triazines and pyrimidines |
WO1998035967A2 (en) | 1997-02-18 | 1998-08-20 | Neurocrine Biosciences, Inc. | Biazacyclic crf antagonists |
NZ335823A (en) * | 1997-04-22 | 2001-06-29 | Neurocrine Biosciences Inc | Thiophenopyridines, preparation as CRF receptor antagonists |
CA2294117A1 (en) * | 1997-07-03 | 1999-01-14 | Dupont Pharmaceuticals Company | Imidazopyrimidines and imidazopyridines for the treatment of neurological disorders |
ATE264860T1 (de) * | 1998-01-28 | 2004-05-15 | Bristol Myers Squibb Pharma Co | Pyrazolotriazine als crf antagonisten |
US6187777B1 (en) * | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
AU3375999A (en) | 1998-04-02 | 1999-10-25 | Neurogen Corporation | Aminoalkyl substituted 5,6,7,8-tetrahydro-9h pyrimidino(2,3-b)indole and 5,6,7,8-tetrahydro-9h-pyrimidino(4,5-b)indole derivatives: crf1 specific ligands |
US6472402B1 (en) | 1998-04-02 | 2002-10-29 | Neurogen Corporation | Aminoalkyl substituted 5,6,7,8-Tetrahydro-9H-Pyridino [2,3-B]indole derivatives |
WO1999051608A1 (en) * | 1998-04-03 | 1999-10-14 | Du Pont Pharmaceuticals Company | THIAZOLO[4,5-d]PYRIMIDINES AND PYRIDINES AS CORTICOTROPIN RELEASING FACTOR (CRF) ANTAGONISTS |
CA2334671A1 (en) | 1998-06-09 | 1999-12-16 | Neurogen Corporation | Pyrido[2,3-b]indolizine derivatives and aza analogues thereof; crf1 specific ligands |
US6509338B1 (en) | 1998-06-22 | 2003-01-21 | Bristol-Myers Squibb Company | Pyrazolo[1,5-A]triazine corticotropin releasing factor antagonists |
EP1105394A1 (de) * | 1998-08-21 | 2001-06-13 | Du Pont Pharmaceuticals Company | Isoxazolo[4,5-d]pyrimidine als crf antagonisten |
IL142893A0 (en) | 1998-11-12 | 2002-04-21 | Neurocrine Biosciences Inc | Fused polyclic heterocyclic compounds and pharmaceutical compositions containing the same |
US6531475B1 (en) * | 1998-11-12 | 2003-03-11 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods relating thereto |
NZ511267A (en) | 1998-11-12 | 2002-12-20 | Neurocrine Biosciences Inc | Tricyclic heterocyclic CRF receptor antagonists and their use in treatment |
WO2000044754A1 (fr) * | 1999-01-29 | 2000-08-03 | Sumitomo Chemical Company, Limited | Agents inhibiteurs d'accumulation de graisse |
EP1040831A3 (de) * | 1999-04-02 | 2003-05-02 | Pfizer Products Inc. | Verwendung von Corticotropin Releasing Factor (CRF) Antagonisten zur Prophylaxe des plötzlichen Todes |
AU4331500A (en) | 1999-04-06 | 2000-10-23 | Du Pont Pharmaceuticals Company | Pyrazolotriazines as crf antagonists |
WO2000059908A2 (en) | 1999-04-06 | 2000-10-12 | Du Pont Pharmaceuticals Company | Pyrazolopyrimidines as crf antagonists |
US6982265B1 (en) | 1999-05-21 | 2006-01-03 | Bristol Myers Squibb Company | Pyrrolotriazine inhibitors of kinases |
EP1669071B1 (de) * | 1999-05-21 | 2009-07-22 | Bristol-Myers Squibb Company | Pyrrolotriazine als Kinase Hemmer. |
US6432989B1 (en) * | 1999-08-27 | 2002-08-13 | Pfizer Inc | Use of CRF antagonists to treat circadian rhythm disorders |
CA2379640C (en) | 1999-09-30 | 2006-11-28 | Neurogen Corporation | Certain alkylene diamine-substituted heterocycles |
IL148905A0 (en) | 1999-09-30 | 2002-09-12 | Neurogen Corp Pfizer Inc | Certain alkylene diamine-substituted pyrazolo{1,5,-a}-1,5-pyrimidines and pyrazolo{1,5,-a}-1,3,5-triazines |
SE9903544D0 (sv) * | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
IL139197A0 (en) | 1999-10-29 | 2001-11-25 | Pfizer Prod Inc | Use of corticotropin releasing factor antagonists and related compositions |
TWI271406B (en) | 1999-12-13 | 2007-01-21 | Eisai Co Ltd | Tricyclic condensed heterocyclic compounds, preparation method of the same and pharmaceuticals comprising the same |
GB2359081A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
GB2359078A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
AU2001232556A1 (en) * | 2000-02-11 | 2001-08-20 | Astrazeneca Ab | Pyrimidine compounds and their use as modulators of chemokine receptor activity |
EP1293213A1 (de) * | 2000-02-14 | 2003-03-19 | Japan Tobacco Inc. | Prophylactische/therapeutische agentia zur behandlung von postchirurgischen stress |
GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
EP1149583A3 (de) * | 2000-04-13 | 2001-11-14 | Pfizer Products Inc. | Kombinationen bestehend aus Antagonisten des Corticotropin freisetzenden Faktors und Stoffen, die die Wachstumshormonsekretion fördern |
JP2003533530A (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 |
AU2001259707A1 (en) | 2000-06-14 | 2001-12-24 | Warner Lambert Company | 6,5-fused bicyclic heterocycles |
US6630476B2 (en) | 2000-07-07 | 2003-10-07 | Bristol-Myers Squibb Pharma Company | Pyrrolo [3,4-d] pyrimidines as corticotropin releasing factor (CRF) antagonists |
SE0003828D0 (sv) | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
US6867300B2 (en) | 2000-11-17 | 2005-03-15 | Bristol-Myers Squibb Company | Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors |
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. |
GB0100624D0 (en) * | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds VII |
TWI312347B (en) | 2001-02-08 | 2009-07-21 | Eisai R&D Man Co Ltd | Bicyclic nitrogen-containing condensed ring compounds |
DK1368094T3 (da) * | 2001-03-13 | 2007-07-02 | Bristol Myers Squibb Pharma Co | 4-(2-Butylamino)-2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl)-pyrazolo[1,5-a]-1,3,5-triazin, dens enantiomerer og farmaceutisk acceptable salte som corticotropin-frigivende faktor-receptor- ligander |
SE0101322D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
ES2366082T3 (es) | 2001-04-27 | 2011-10-17 | EISAI R&D MANAGEMENT CO., LTD. | Pirazolo 1,5-a piridinas y medicinas que las contienen. |
CA2450535A1 (en) * | 2001-05-21 | 2002-11-28 | Neurocrine Biosciences Inc. | Tri-and tetraaza-acenaphthylen derivatives as crf receptor antagonists |
GB0117396D0 (en) * | 2001-07-17 | 2001-09-05 | Glaxo Group Ltd | Chemical compounds |
EP2335700A1 (de) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C Virus Polymerase Inhibitoren mit heterobicylischer Struktur |
TW200300350A (en) | 2001-11-14 | 2003-06-01 | Bristol Myers Squibb Co | C-5 modified indazolylpyrrolotriazines |
AU2003217712A1 (en) | 2002-03-07 | 2003-09-22 | Smithkline Beecham Corporation | Pyrazolopyrimidine and pyrazolotriazine derivatives and pharmaceutical compositions containing them |
DK1348707T3 (da) * | 2002-03-28 | 2010-12-13 | Ustav Ex Botan Av Cr V V I Inst Of Ex Botany Academy Of Sciences Of The Czech Republic Pro | Pyrazolo[4,3-d]pyrimidiner, fremgangsmåder til deres fremstilling samt deres terapeutiske anvendelse |
US7119200B2 (en) * | 2002-09-04 | 2006-10-10 | Schering Corporation | Pyrazolopyrimidines as cyclin dependent kinase inhibitors |
GB0221828D0 (en) | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
AR041470A1 (es) | 2002-10-17 | 2005-05-18 | Upjohn Co | Compuestos de pirrolo (1,2 - b) piridazina y sus usos |
RU2327699C2 (ru) | 2002-10-22 | 2008-06-27 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Соединения 7-фенилпиразолопиридина |
US7176216B2 (en) | 2002-10-22 | 2007-02-13 | Eisai Co., Ltd. | 7-phenylpyrazolopyridine compounds |
TW200420565A (en) | 2002-12-13 | 2004-10-16 | Bristol Myers Squibb Co | C-6 modified indazolylpyrrolotriazines |
ES2295816T3 (es) | 2003-01-14 | 2008-04-16 | Arena Pharmaceuticals, Inc. | Derivados arilo y heteroarilo 1,2,3-trisustituidos como moduladores del metabolismo, y profilaxis y tratamiento de transtornos relacionados con los mismos, tales como la diabetes y la hiperglucemia. |
US7041671B2 (en) * | 2003-04-02 | 2006-05-09 | Pfizer Inc | Pyrrolo[1,2-b]pyridazine compounds and their uses |
US7056920B2 (en) * | 2003-04-04 | 2006-06-06 | Pfizer Inc | Pyrrolo[1,2-B]pyridazine compounds and their uses |
US7034023B2 (en) | 2003-04-04 | 2006-04-25 | Pfizer Inc | Pyrrolo[1,2-B]pyridazine compounds and their uses |
GB0308208D0 (en) | 2003-04-09 | 2003-05-14 | Glaxo Group Ltd | Chemical compounds |
EP1615929A1 (de) * | 2003-04-15 | 2006-01-18 | Pharmacia & Upjohn Company LLC | Pyrrolo[1,2-b]pyridazin-verbindungen und ihre verwendungen |
EP1620437B1 (de) | 2003-04-29 | 2009-06-17 | Pfizer Limited | 5,7-diaminopyrazolo¬4,3-d pyrimidine zur verwendung in der behandlung von bluthochdruck |
WO2004099213A2 (en) * | 2003-05-07 | 2004-11-18 | Pharmacia & Upjohn Company Llc | Pyrrolo (1,2-b) pyridazine compounds and their use as crf-1 receptor antagonists |
WO2004110454A1 (ja) * | 2003-06-13 | 2004-12-23 | Ishihara Sangyo Kaisha, Ltd. | アデノシンA2a受容体アゴニストの投与が必要な疾患を治療又は予防するための組成物 |
CA2532971A1 (en) * | 2003-07-14 | 2005-01-27 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
EP1680424A2 (de) * | 2003-09-05 | 2006-07-19 | Neurogen Corporation | Heteroarylkondensierte pyridine, pyrazine und pyrimidine als crf1-rezeptorliganden |
US7153961B2 (en) | 2003-11-25 | 2006-12-26 | Bristol-Myers Squibb Pharma Co. | Salt and crystalline form thereof of a corticotropin releasing factor receptor antagonist |
US7208596B2 (en) | 2003-11-25 | 2007-04-24 | Bristol-Myers Squibb Pharma Company | Processes for the preparation of pyrazolo[1,5-a]-1,3,5-triazines and intermediates thereof |
GB0328243D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
US7102001B2 (en) | 2003-12-12 | 2006-09-05 | Bristol-Myers Squibb Company | Process for preparing pyrrolotriazine |
NZ547990A (en) | 2003-12-22 | 2010-04-30 | Smithkline Beecham Cork Ltd | CRF receptor antagonists and methods relating thereto |
MY145634A (en) | 2003-12-29 | 2012-03-15 | Bristol Myers Squibb Co | Pyrrolotriazine compounds as kinase inhibitors |
US7064203B2 (en) | 2003-12-29 | 2006-06-20 | Bristol Myers Squibb Company | Di-substituted pyrrolotriazine compounds |
JP2007517793A (ja) | 2004-01-06 | 2007-07-05 | 大正製薬株式会社 | 環状アミノ基によって置換されたチエノピリミジン及びチエノピリジン誘導体 |
CA2552503C (en) * | 2004-01-06 | 2011-09-13 | Taisho Pharmaceutical Co., Ltd. | Pyrrolopyrimidine and pyrrolotriazine derivatives |
US7582770B2 (en) | 2004-02-20 | 2009-09-01 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US7102002B2 (en) | 2004-06-16 | 2006-09-05 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
US7102003B2 (en) | 2004-07-01 | 2006-09-05 | Bristol-Myers Squibb Company | Pyrrolotriazine compounds |
US7504521B2 (en) | 2004-08-05 | 2009-03-17 | Bristol-Myers Squibb Co. | Methods for the preparation of pyrrolotriazine compounds |
TW200618803A (en) | 2004-08-12 | 2006-06-16 | Bristol Myers Squibb Co | Process for preparing pyrrolotriazine aniline compounds useful as kinase inhibitors |
GB0519957D0 (en) | 2005-09-30 | 2005-11-09 | Sb Pharmco Inc | Chemical compound |
ATE430746T1 (de) * | 2004-10-19 | 2009-05-15 | Smithkline Beecham Cork Ltd | Crf-rezeptor-antagonisten und zugehörige verfahren |
US7151176B2 (en) | 2004-10-21 | 2006-12-19 | Bristol-Myers Squibb Company | Pyrrolotriazine compounds |
EP1814561A4 (de) | 2004-10-29 | 2012-12-19 | Biocryst Pharm Inc | Therapeutische furopyrimidine und thienopyrimidine |
US7674822B2 (en) | 2004-11-24 | 2010-03-09 | Wyeth | PTP1b inhibitors |
EP1863500A2 (de) | 2005-03-29 | 2007-12-12 | Biocryst Pharmaceuticals, Inc. | Hepatitis-c-therapien |
EP1903045A1 (de) * | 2005-05-27 | 2008-03-26 | Mitsubishi Tanabe Pharma Corporation | Pyrazolopyrimidinderivat |
TW200740820A (en) | 2005-07-05 | 2007-11-01 | Takeda Pharmaceuticals Co | Fused heterocyclic derivatives and use thereof |
WO2007013964A1 (en) | 2005-07-22 | 2007-02-01 | Sunesis Pharmaceuticals, Inc. | Pyrazolo pyrimidines useful as aurora kinase inhibitors |
US20070078136A1 (en) | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
US7514435B2 (en) | 2005-11-18 | 2009-04-07 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
US8063208B2 (en) | 2006-02-16 | 2011-11-22 | Bristol-Myers Squibb Company | Crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol |
US8110580B2 (en) | 2006-09-20 | 2012-02-07 | Eli Lilly And Company | Thiophene pyrazolopyrimidine compounds |
KR101088239B1 (ko) | 2006-09-20 | 2011-11-30 | 일라이 릴리 앤드 캄파니 | Crf1 수용체 길항제로서의 티아졸 피라졸로피리미딘 |
JP5513118B2 (ja) | 2006-10-19 | 2014-06-04 | シグナル ファーマシューティカルズ,エルエルシー | ヘテロアリール化合物、その組成物、及びプロテインキナーゼ阻害剤としてのそれらの使用 |
NZ586662A (en) | 2007-12-19 | 2012-08-31 | Vertex Pharma | PYRAZOLO[1,5-a]PYRIMIDINES USEFUL AS JANUS KINASE 2 INHIBITORS |
WO2009126861A2 (en) | 2008-04-11 | 2009-10-15 | Bristol-Myers Squibb Company | Triazolopyridine compounds useful as dgat1 inhibitors |
US8324241B2 (en) | 2008-04-11 | 2012-12-04 | Bristol-Myers Squibb Company | Triazolo compounds useful as DGAT1 inhibitors |
PT2266990E (pt) | 2008-04-15 | 2012-12-27 | Eisai R&D Man Co Ltd | Composto de 3-fenilpirazolo[5,1-b]tiazole |
GB0906579D0 (en) | 2009-04-16 | 2009-05-20 | Vernalis R&D Ltd | Pharmaceuticals, compositions and methods of making and using the same |
TWI491610B (zh) | 2008-10-09 | 2015-07-11 | 必治妥美雅史谷比公司 | 作為激酶抑制劑之咪唑并嗒腈 |
AR078521A1 (es) | 2009-10-08 | 2011-11-16 | Eisai R&D Man Co Ltd | Compuesto pirazolotiazol |
US20130065883A1 (en) * | 2010-02-18 | 2013-03-14 | Centro Nacional de Investigaceiones Oncologicas (CNIO) | Triazolo [4, 5- B] Pyridin Derivatives |
US8912184B1 (en) | 2010-03-01 | 2014-12-16 | Alzheimer's Institute Of America, Inc. | Therapeutic and diagnostic methods |
WO2011130481A1 (en) * | 2010-04-16 | 2011-10-20 | Abbott Laboratories | Pyrrolopyrazinone inhibitors of kinases |
CN102971326A (zh) | 2010-04-28 | 2013-03-13 | 百时美施贵宝公司 | 咪唑并哒嗪化合物及其在癌症中的用途 |
TWI541243B (zh) | 2010-09-10 | 2016-07-11 | 拜耳知識產權公司 | 經取代咪唑并嗒 |
WO2012040279A1 (en) | 2010-09-22 | 2012-03-29 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
WO2012064815A1 (en) | 2010-11-12 | 2012-05-18 | Bristol-Myers Squibb Company | Substituted azaindazole compounds |
CN103415518A (zh) | 2010-12-17 | 2013-11-27 | 拜耳知识产权有限责任公司 | 在过度增殖性病症的治疗中用作mps-1和tkk抑制剂的咪唑并吡嗪 |
CN103370322B (zh) | 2010-12-17 | 2016-02-10 | 拜耳知识产权有限责任公司 | 在过度增殖性病症的治疗中用作mps-1和tkk抑制剂的2-取代的咪唑并吡嗪 |
EP2651944B1 (de) | 2010-12-17 | 2015-09-23 | Bayer Intellectual Property GmbH | Substituierte 6-imidazopyrazines zur verwendung als mps-1 und tkk-inhibitoren zur behandlung von hyperproliferativen erkrankungen |
ES2887303T3 (es) | 2011-04-08 | 2021-12-22 | Janssen Sciences Ireland Unlimited Co | Derivados de pirimidina para el tratamiento de infecciones víricas |
WO2012149157A2 (en) * | 2011-04-26 | 2012-11-01 | Bioenergenix | Heterocyclic compounds for the inhibition of pask |
US8969586B2 (en) | 2011-09-27 | 2015-03-03 | Bristol-Myers Squibb Company | Substituted bicyclic heteroaryl compounds |
MX347596B (es) | 2011-11-09 | 2017-05-03 | Janssen Sciences Ireland Uc | Derivados de purina para el tratamiento de infecciones viricas. |
ES2605946T3 (es) | 2012-03-14 | 2017-03-17 | Bayer Intellectual Property Gmbh | Imidazopiridazinas sustituidas |
WO2014009305A1 (en) * | 2012-07-09 | 2014-01-16 | Janssen Pharmaceutica Nv | Inhibitors of phosphodiesterase 10 enzyme |
JP6250046B2 (ja) | 2012-07-13 | 2017-12-20 | ヤンセン・サイエンシズ・アイルランド・ユーシー | ウイルス感染症の処置のための大環状プリン |
WO2014020041A1 (en) | 2012-08-02 | 2014-02-06 | Bayer Pharma Aktiengesellschaft | Combinations for the treatment of cancer |
BR112015007586B1 (pt) | 2012-10-10 | 2021-02-09 | Janssen Sciences Ireland Uc | derivados de pirrolo[3,2-d]pirimidina, seu uso e composição farmacêutica que os compreende |
WO2014066795A1 (en) | 2012-10-25 | 2014-05-01 | Bioenergenix | Heterocyclic compounds for the inhibition of pask |
WO2014066743A1 (en) | 2012-10-25 | 2014-05-01 | Bioenergenix | Heterocyclic compounds for the inhibition of pask |
DK2925729T3 (en) | 2012-11-16 | 2018-01-22 | Janssen Sciences Ireland Uc | HETEROCYCLIC SUBSTITUTED 2-AMINOQUINAZOLINE DERIVATIVES FOR TREATING VIRUS INFECTIONS |
AU2014220717B2 (en) | 2013-02-21 | 2018-03-29 | Janssen Sciences Ireland Uc | 2-aminopyrimidine derivatives for the treatment of viral infections |
BR112015022545A2 (pt) | 2013-03-13 | 2017-07-18 | Constellation Pharmaceuticals Inc | compostos de pirazolo e os usos disso |
MX366481B (es) | 2013-03-29 | 2019-07-09 | Janssen Sciences Ireland Uc | Deaza-purinonas macrociclicas para el tratamiento de infecciones virales. |
EA034674B1 (ru) | 2013-05-24 | 2020-03-05 | Янссен Сайенсиз Айрлэнд Юси | Производные пиридона для лечения нарушений, в которое вовлечены модуляции tlr7 и/или tlr8 |
CN105377848A (zh) | 2013-06-11 | 2016-03-02 | 拜耳制药股份公司 | 取代的三唑并吡啶的前体药物衍生物 |
UA117590C2 (uk) * | 2013-06-27 | 2018-08-27 | ЯНССЕН САЙЄНСЕЗ АЙРЛЕНД ЮСі | ПОХІДНІ ПІРОЛО[3,2-d]ПІРИМІДИНУ ДЛЯ ЛІКУВАННЯ ВІРУСНИХ ІНФЕКЦІЙ ТА ІНШИХ ЗАХВОРЮВАНЬ |
EA036162B1 (ru) | 2013-07-30 | 2020-10-08 | Янссен Сайенсиз Айрлэнд Юси | Производные тиено[3,2-d]пиримидинов для лечения вирусных инфекций |
EP2940022B1 (de) | 2014-04-30 | 2020-09-02 | Masarykova Univerzita | Furopyridinen als Inhibitoren von Proteinkinasen |
NZ734220A (en) | 2015-01-06 | 2022-01-28 | Arena Pharm Inc | Methods of treating conditions related to the s1p1 receptor |
MA42807A (fr) | 2015-06-22 | 2018-07-25 | Arena Pharm Inc | Sel l-arginine cristallin d'acide (r)-2-(7-(4-cyclopentyl-3-(trifluorométhyl)benzyloxy)-1,2,3,4-tétrahydrocyclo-penta[b]indol-3-yl)acétique (composé 1) pour une utilisation dans des troubles associés au récepteur de s1p1 |
RU2699568C2 (ru) * | 2015-12-21 | 2019-09-06 | Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова" | Лиганды транслокаторного белка TSPO, обладающие антидепрессивной и ноотропной активностью |
WO2018002319A1 (en) | 2016-07-01 | 2018-01-04 | Janssen Sciences Ireland Uc | Dihydropyranopyrimidines for the treatment of viral infections |
SG10202010317VA (en) | 2016-09-29 | 2020-11-27 | Janssen Sciences Ireland Unlimited Co | Pyrimidine prodrugs for the treatment of viral infections and further diseases |
TW201945003A (zh) | 2018-03-01 | 2019-12-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | 2,4-二胺基喹唑啉衍生物及其醫學用途 |
CN108812546A (zh) * | 2018-09-07 | 2018-11-16 | 四川省草原科学研究院 | 适于青藏高原地区牦牛运输减少应激的药物及使用方法 |
KR20240023691A (ko) | 2020-08-12 | 2024-02-22 | 스프루스 바이오사이언시스 인코포레이티드 | 다낭성 난소 증후군을 치료하기 위한 방법 및 조성물 |
US11708372B2 (en) | 2021-11-19 | 2023-07-25 | Spruce Biosciences, Inc. | Crystalline composition of tildacerfont and methods of use and preparation thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
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TW574214B (en) * | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
CA2194756A1 (en) * | 1995-05-12 | 1996-11-14 | Jun Yuan | Novel deazapurine derivatives; a new class of crf1 specific ligands |
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