CA2902132C - Quinazolines as kinase inhibitors - Google Patents
Quinazolines as kinase inhibitors Download PDFInfo
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- CA2902132C CA2902132C CA2902132A CA2902132A CA2902132C CA 2902132 C CA2902132 C CA 2902132C CA 2902132 A CA2902132 A CA 2902132A CA 2902132 A CA2902132 A CA 2902132A CA 2902132 C CA2902132 C CA 2902132C
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- disease
- compound
- pharmaceutically acceptable
- sarcoidosis
- tert
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Classifications
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Landscapes
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| US61/767,423 | 2013-02-21 | ||
| PCT/IB2014/059094 WO2014128622A1 (en) | 2013-02-21 | 2014-02-19 | Quinazolines as kinase inhibitors |
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| CA2902132A1 CA2902132A1 (en) | 2014-08-28 |
| CA2902132C true CA2902132C (en) | 2020-09-22 |
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| WO2012122011A2 (en) | 2011-03-04 | 2012-09-13 | Glaxosmithkline Llc | Amino-quinolines as kinase inhibitors |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| TW201425307A (zh) | 2012-09-13 | 2014-07-01 | Glaxosmithkline Llc | 作為激酶抑制劑之胺基－喹啉類 |
| TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
| TWI630203B (zh) | 2013-02-21 | 2018-07-21 | 葛蘭素史克智慧財產發展有限公司 | 做為激酶抑制劑的喹唑啉類 |
| GB201506872D0 (en) | 2015-04-22 | 2015-06-03 | Ge Oil & Gas Uk Ltd | Novel compounds |
| GB201516243D0 (en) | 2015-09-14 | 2015-10-28 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CA3020792A1 (en) | 2016-04-20 | 2017-10-26 | Glaxosmithkline Intellectual Property Development Limited | Conjugates comprising ripk2 inhibitors |
| CN112638905A (zh) * | 2018-08-28 | 2021-04-09 | 南京明德新药研发有限公司 | 作为rip2激酶抑制剂的喹唑啉类衍生物 |
| WO2025092821A1 (zh) * | 2023-11-01 | 2025-05-08 | 成都赜灵生物医药科技有限公司 | 喹唑啉衍生物类ripk2抑制剂及其用途 |
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| US4916135A (en) | 1989-05-08 | 1990-04-10 | Hoechst Roussel Pharmaceuticals Inc. | N-heteroaryl-4-quinolinamines |
| US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| PT100905A (pt) | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
| GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US6046206A (en) | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having a precancerous lesions with amide quinazoline derivatives |
| DE69716916T2 (de) | 1996-07-13 | 2003-07-03 | Glaxo Group Ltd., Greenford | Kondensierte heterozyklische verbindungen als protein kinase inhibitoren |
| AU3969697A (en) | 1996-08-01 | 1998-02-25 | Dow Agrosciences Llc | Quinolinium derivatives having fungicidal activity |
| AU733551B2 (en) | 1996-09-25 | 2001-05-17 | Astrazeneca Ab | Qinoline derivatives inhibiting the effect of growth factors such as VEGF |
| UA73073C2 (uk) | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| DK1117653T3 (da) | 1998-10-01 | 2003-05-26 | Astrazeneca Ab | Quinolin- og quinazolinderivater og deres anvendelse som inhibitorer af cykokin-merierede sygdomme |
| GB2345486A (en) | 1999-01-11 | 2000-07-12 | Glaxo Group Ltd | Heteroaromatic protein tyrosine kinase inhibitors |
| SK3822002A3 (en) | 1999-09-21 | 2002-10-08 | Astrazeneca Ab | Quinazoline derivatives, process for the preparation thereof and their use |
| JP2003520855A (ja) | 2000-01-28 | 2003-07-08 | アストラゼネカ アクチボラグ | 化学的化合物 |
| HUP0301117A3 (en) | 2000-02-17 | 2004-01-28 | Amgen Inc Thousand Oaks | Imidazole derivatives kinase inhibitors, their use, process for their preparation and pharmaceutical compositions containing them |
| US6521618B2 (en) | 2000-03-28 | 2003-02-18 | Wyeth | 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors |
| US6589758B1 (en) | 2000-05-19 | 2003-07-08 | Amgen Inc. | Crystal of a kinase-ligand complex and methods of use |
| CN1315822C (zh) | 2000-08-09 | 2007-05-16 | 阿斯特拉曾尼卡有限公司 | 具有vegf抑制活性的喹啉衍生物 |
| US6548508B2 (en) | 2000-10-20 | 2003-04-15 | Pfizer, Inc. | Use of PDE V inhibitors for improved fecundity in mammals |
| GB0104422D0 (en) | 2001-02-22 | 2001-04-11 | Glaxo Group Ltd | Quinoline derivative |
| JP4329003B2 (ja) | 2001-03-23 | 2009-09-09 | バイエル コーポレイション | Ｒｈｏキナーゼ阻害剤 |
| TWI336328B (en) | 2001-03-23 | 2011-01-21 | Bayer Healthcare Llc | Rho-kinase inhibitors |
| SE0101675D0 (sv) | 2001-05-11 | 2001-05-11 | Astrazeneca Ab | Novel composition |
| US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-substituted pyrimidinyl derivatives and methods of use |
| WO2003026664A1 (en) | 2001-09-26 | 2003-04-03 | Bayer Corporation | 2-phenylamino-4- (5-pyrazolylamino) -pyramidine derivatives as kinase inhibitors, in particular, src kinase inhibitors |
| KR101029281B1 (ko) | 2001-12-24 | 2011-04-18 | 아스트라제네카 아베 | 오로라 키나제의 억제제로서 치환된 퀴나졸린 유도체 |
| US7645878B2 (en) | 2002-03-22 | 2010-01-12 | Bayer Healthcare Llc | Process for preparing quinazoline Rho-kinase inhibitors and intermediates thereof |
| TWI275390B (en) | 2002-04-30 | 2007-03-11 | Wyeth Corp | Process for the preparation of 7-substituted-3- quinolinecarbonitriles |
| AU2003255482A1 (en) * | 2002-10-02 | 2004-04-23 | Merck Patent Gmbh | Use of 4 amino-quinazolines as anti cancer agents |
| WO2004037814A1 (en) | 2002-10-25 | 2004-05-06 | Vertex Pharmaceuticals Incorporated | Indazolinone compositions useful as kinase inhibitors |
| US20040122161A1 (en) | 2002-12-21 | 2004-06-24 | Paul Charles W. | Hot melt adhesive based on acrylic block copolymers |
| RU2350611C1 (ru) * | 2002-12-24 | 2009-03-27 | Астразенека Аб | Производные фосфонооксихиназолина и их фармацевтическое применение |
| UA86470C2 (ru) * | 2002-12-24 | 2009-04-27 | Астразенека Аб | Производные фосфонооксихиназолина и их фармацевтическое применение |
| TWI328009B (en) | 2003-05-21 | 2010-08-01 | Glaxo Group Ltd | Quinoline derivatives as phosphodiesterase inhibitors |
| MXPA05012839A (es) | 2003-05-27 | 2006-05-17 | Pfizer Prod Inc | Quinazolinas y pirido[3,4-d] pirimidinas como inhibidores de receptores tirosina quinasa. |
| WO2005003100A2 (en) | 2003-07-03 | 2005-01-13 | Myriad Genetics, Inc. | 4-arylamino-quinazolines as activators of caspases and inducers of apoptosis |
| DK1667991T3 (da) | 2003-09-16 | 2008-08-18 | Astrazeneca Ab | Quinazolinderivater som tyrosinkinaseinhibitorer |
| CA2744997A1 (en) | 2003-09-26 | 2005-04-07 | Exelixis, Inc. | C-met modulators and method of use |
| AU2005249503B2 (en) | 2003-11-10 | 2011-08-25 | Vertex Pharmaceuticals Incorporated | ICE inhibitors for the treatment of autoinflammatory diseases |
| JP4503022B2 (ja) | 2003-12-23 | 2010-07-14 | ファイザー・インク | 新規キノリン誘導体 |
| AU2005223610B2 (en) | 2004-03-23 | 2008-05-29 | Banyu Pharmaceutical Co., Ltd. | Substituted quinazoline or pyridopyrimidine derivative |
| US20070299092A1 (en) | 2004-05-20 | 2007-12-27 | Wyeth | Quinone Substituted Quinazoline and Quinoline Kinase Inhibitors |
| CA2569404A1 (en) | 2004-06-04 | 2005-12-22 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| FR2873695A1 (fr) | 2004-07-30 | 2006-02-03 | Palumed Sa | Molecules hybrides qa ou q est une aminoquinoleine et a est un antibiotique ou un inhibiteur de resistance), leur synthese et leurs utilisations en tant qu'agent antibacterien |
| JP2008519083A (ja) * | 2004-11-09 | 2008-06-05 | エフ．ホフマン−ラ ロシュ アーゲー | アミノキナゾリン化合物 |
| WO2006066955A1 (de) | 2004-12-22 | 2006-06-29 | Bayer Schering Pharma Aktiengesellschaft | Chinolinderivat, dessen verwendung, herstellung und dieses enthaltendes arzneimittel |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| JP2008537748A (ja) | 2005-04-06 | 2008-09-25 | エクセリクシス、インコーポレイテッド | ｃ−Ｍｅｔモジュレーター及び使用方法 |
| JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| EP1746096A1 (en) | 2005-07-15 | 2007-01-24 | 4Sc Ag | 2-Arylbenzothiazole analogues and uses thereof in the treatment of cancer |
| ITMI20052008A1 (it) | 2005-10-21 | 2007-04-22 | Ctg Pharma S R L | Nuovi antimalarici derivati della 4-aminochinolina |
| FR2902100A1 (fr) | 2006-06-13 | 2007-12-14 | Sanofi Aventis Sa | Molecules duales contenant un derive peroxydique, leur synthese et leurs applications en therapeutique |
| US7511063B2 (en) | 2006-08-16 | 2009-03-31 | Schering Corporation | High affinity quinoline-based kinase ligands |
| JP2008063278A (ja) | 2006-09-07 | 2008-03-21 | Fujifilm Finechemicals Co Ltd | １−ピリジン−４−イル−インドール類の製造方法 |
| US8604044B2 (en) | 2006-09-11 | 2013-12-10 | Curis, Inc. | Quinazoline based EGFR inhibitors containing a zinc binding moiety |
| EP2061469B8 (en) | 2006-09-11 | 2014-02-26 | Curis, Inc. | Quinazoline based egfr inhibitors |
| US20080221132A1 (en) | 2006-09-11 | 2008-09-11 | Xiong Cai | Multi-Functional Small Molecules as Anti-Proliferative Agents |
| TW200829555A (en) | 2006-11-10 | 2008-07-16 | Astrazeneca Ab | Chemical compounds |
| US8163923B2 (en) | 2007-03-14 | 2012-04-24 | Advenchen Laboratories, Llc | Spiro substituted compounds as angiogenesis inhibitors |
| US8148532B2 (en) | 2007-03-14 | 2012-04-03 | Guoqing Paul Chen | Spiro substituted compounds as angiogenesis inhibitors |
| US20080234267A1 (en) | 2007-03-20 | 2008-09-25 | Karen Elizabeth Lackey | Compounds and Methods of Treatment |
| WO2008119771A2 (en) | 2007-03-30 | 2008-10-09 | Clanotech Ab | Quinoline-s-carboxylic acid derivatives as tyrosine kinase inhibitors |
| CA2684644A1 (en) | 2007-04-23 | 2008-10-30 | Sanofi-Aventis | Quinoline-carboxamide derivatives as p2y12 antagonists |
| PE20090717A1 (es) | 2007-05-18 | 2009-07-18 | Smithkline Beecham Corp | Derivados de quinolina como inhibidores de la pi3 quinasa |
| TW200908982A (en) | 2007-06-01 | 2009-03-01 | Wyeth Corp | Treatment of imatinib resistant leukemia |
| CN101362719B (zh) | 2007-08-06 | 2012-04-18 | 北京师范大学 | 喹啉类衍生物以及包含其的组合物 |
| US7939546B2 (en) | 2007-10-12 | 2011-05-10 | Supergen, Inc. | Quinoline derivatives for modulating DNA methylation |
| US7790746B2 (en) | 2007-10-12 | 2010-09-07 | Supergen, Inc. | Quinoline derivatives for modulating DNA methylation |
| EP2072502A1 (de) | 2007-12-20 | 2009-06-24 | Bayer Schering Pharma Aktiengesellschaft | Sulfoximid-substituierte Chinolin- und Chinazolinderivate als Kinase-Inhibitoren |
| GB0801416D0 (en) | 2008-01-25 | 2008-03-05 | Piramed Ltd | Pharmaceutical compounds |
| MX2010009669A (es) | 2008-03-06 | 2010-09-22 | Genentech Inc | Terapia de combinacion con antagonistas de c-met y egfr. |
| BRPI0915240A2 (pt) | 2008-10-17 | 2016-02-16 | Genentech Inc | método para tratar câncer, método para avaliação de um paciente submetido ao tratamento de câncer, método para avaliação de um paciente que tem ou com suspeita de ter câncer e uso de um anticorpo anti-c-met |
| DE102008062566A1 (de) | 2008-12-16 | 2010-06-17 | Bayer Schering Pharma Aktiengesellschaft | Aminosäureester-Prodrugs und ihre Verwendung |
| PH12012500097A1 (en) | 2009-07-21 | 2011-01-27 | Shanghai Inst Organic Chem | Potent small molecule inhibitors of autophagy, and methods of use thereof |
| US20130005726A1 (en) | 2010-03-08 | 2013-01-03 | Derek Abbott | Compositions and methods for treating inflammatory disorders |
| US20130023532A1 (en) | 2010-03-26 | 2013-01-24 | Casillas Linda N | Indazolyl-pyrimidines as kinase inhibitors |
| JP2013523658A (ja) | 2010-03-26 | 2013-06-17 | グラクソ グループ リミテッド | キナーゼ阻害剤としてのピラゾリル‐ピリミジン |
| EP2552208A4 (en) | 2010-03-31 | 2014-07-09 | Glaxo Group Ltd | IMIDAZOLYL-IMIDAZOLES AS KINASE INHIBITORS |
| ES2552977T3 (es) | 2010-05-07 | 2015-12-03 | Glaxosmithkline Intellectual Property Development Limited | Amino-quinolinas como inhibidores de quinasa |
| UY33549A (es) | 2010-08-10 | 2012-01-31 | Glaxo Group Ltd | Quinolil aminas como agentes inhibidores de las quinasas |
| WO2012027495A1 (en) * | 2010-08-27 | 2012-03-01 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
| RU2568258C2 (ru) | 2011-02-28 | 2015-11-20 | Саншайн Лейк Фарма Ко., Лтд | Замещенные соединения хинолина и способы их использования |
| WO2012122011A2 (en) | 2011-03-04 | 2012-09-13 | Glaxosmithkline Llc | Amino-quinolines as kinase inhibitors |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
| TW201425307A (zh) | 2012-09-13 | 2014-07-01 | Glaxosmithkline Llc | 作為激酶抑制劑之胺基－喹啉類 |
| TWI630203B (zh) | 2013-02-21 | 2018-07-21 | 葛蘭素史克智慧財產發展有限公司 | 做為激酶抑制劑的喹唑啉類 |
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- 2014-02-19 ES ES14708681.3T patent/ES2654100T3/es active Active
- 2014-02-19 WO PCT/IB2014/059094 patent/WO2014128622A1/en not_active Ceased
- 2014-02-19 AU AU2014220300A patent/AU2014220300B2/en not_active Ceased
- 2014-02-19 RU RU2015139758A patent/RU2662810C2/ru not_active IP Right Cessation
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- 2014-02-19 BR BR112015019624A patent/BR112015019624A2/pt not_active Application Discontinuation
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Also Published As
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|---|---|
| TW201444824A (zh) | 2014-12-01 |
| ES2654100T3 (es) | 2018-02-12 |
| JP2016509051A (ja) | 2016-03-24 |
| EP2958911A1 (en) | 2015-12-30 |
| EP2958911B1 (en) | 2017-10-18 |
| KR20150118152A (ko) | 2015-10-21 |
| AR094707A1 (es) | 2015-08-19 |
| TWI630203B (zh) | 2018-07-21 |
| RU2015139758A (ru) | 2017-03-24 |
| US9650364B2 (en) | 2017-05-16 |
| CA2902132A1 (en) | 2014-08-28 |
| CN105143208B (zh) | 2017-09-26 |
| CN105143208A (zh) | 2015-12-09 |
| BR112015019624A2 (pt) | 2017-07-18 |
| RU2662810C2 (ru) | 2018-07-31 |
| AU2014220300A1 (en) | 2015-08-06 |
| JP6301374B2 (ja) | 2018-03-28 |
| US20150361069A1 (en) | 2015-12-17 |
| WO2014128622A1 (en) | 2014-08-28 |
| AU2014220300B2 (en) | 2016-10-13 |
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