JP5746172B2 - ホスホイノシチド３−キナーゼ阻害剤としての三環式複素環化合物 - Google Patents
ホスホイノシチド３−キナーゼ阻害剤としての三環式複素環化合物 Download PDFInfo
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- JP5746172B2 JP5746172B2 JP2012525212A JP2012525212A JP5746172B2 JP 5746172 B2 JP5746172 B2 JP 5746172B2 JP 2012525212 A JP2012525212 A JP 2012525212A JP 2012525212 A JP2012525212 A JP 2012525212A JP 5746172 B2 JP5746172 B2 JP 5746172B2
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| AR095443A1 (es) * | 2013-03-15 | 2015-10-14 | Fundación Centro Nac De Investig Oncológicas Carlos Iii | Heterociclos condensados con acción sobre atr |
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| CN104557955B (zh) * | 2013-10-23 | 2017-05-03 | 上海汇伦生命科技有限公司 | 作为PI3K/mTOR抑制剂的三环类化合物，其制备方法和用途 |
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| MY196817A (en) | 2015-12-16 | 2023-05-03 | Genentech Inc | Process for the preparation of tricyclic pi3k inhibitor compounds and methods for using the same for the treatment of cancer |
| BR112018003417B1 (pt) | 2016-06-22 | 2023-10-24 | Vanderbilt University | Composto modulador alostérico positivo do receptor muscarínico de acetilcolina m4 e composição farmacêutica que o compreende |
| TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| US10961253B2 (en) | 2016-11-07 | 2021-03-30 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor M4 |
| EP3544961B1 (en) | 2016-11-07 | 2021-08-18 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor m4 |
| WO2018085803A1 (en) | 2016-11-07 | 2018-05-11 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor m4 |
| GB201702938D0 (en) | 2017-02-23 | 2017-04-12 | Univ Southampton | Methods of generating and screening compartmentalised peptides libraries |
| US11376254B2 (en) | 2017-12-05 | 2022-07-05 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor M4 |
| TW201930311A (zh) | 2017-12-05 | 2019-08-01 | 泛德比爾特大學 | 蕈毒鹼型乙醯膽鹼受體m4之正向別構調節劑 |
| KR20200108301A (ko) | 2018-01-10 | 2020-09-17 | 리커리엄 아이피 홀딩스, 엘엘씨 | 벤즈아미드 화합물 |
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Family Cites Families (47)
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|---|---|---|---|---|
| DE1445742A1 (de) | 1963-11-06 | 1968-12-19 | Bayer Ag | Verfahren zur Herstellung von 2-Stellung substituierten Benzoxazinonen |
| US4017500A (en) | 1973-07-16 | 1977-04-12 | Schering Corporation | Certain 8-amino-1,7-naphthyridines |
| US5703075A (en) | 1988-12-21 | 1997-12-30 | Pharmacia & Upjohn Company | Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones |
| US6608053B2 (en) * | 2000-04-27 | 2003-08-19 | Yamanouchi Pharmaceutical Co., Ltd. | Fused heteroaryl derivatives |
| KR100774855B1 (ko) * | 2000-04-27 | 2007-11-08 | 아스텔라스세이야쿠 가부시키가이샤 | 축합 헤테로아릴 유도체 |
| WO2002002551A1 (en) | 2000-06-30 | 2002-01-10 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| US6905669B2 (en) | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
| US7576074B2 (en) | 2002-07-15 | 2009-08-18 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
| FR2846657B1 (fr) | 2002-11-05 | 2004-12-24 | Servier Lab | Nouveaux composes pyridopyrimidinone, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CA2557541C (en) | 2004-02-26 | 2014-12-16 | Aska Pharmaceutical Co., Ltd. | Pyrimidine derivatives |
| GB0423653D0 (en) | 2004-10-25 | 2004-11-24 | Piramed Ltd | Pharmaceutical compounds |
| EP2354140A1 (en) | 2005-05-20 | 2011-08-10 | Vertex Pharmaceuticals Incorporated | Pyrrolopyridines useful as inhibitors of protein kinase |
| WO2007084667A2 (en) | 2006-01-19 | 2007-07-26 | Osi Pharmaceutical, Inc. | Fused heterobicyclic kinase inhibitors |
| TW200801012A (en) * | 2006-04-26 | 2008-01-01 | Piramed Ltd | Phosphoinositide 3-kinase inhibitor compounds and methods of use |
| KR20090021155A (ko) | 2006-04-26 | 2009-02-27 | 에프. 호프만-라 로슈 아게 | Ｐｉ3ｋ 억제제로서의 피리미딘 유도체 |
| WO2008001076A1 (en) | 2006-06-26 | 2008-01-03 | Ucb Pharma S.A. | Fused thiazole derivatives as kinase inhibitors |
| KR20090087027A (ko) | 2006-11-13 | 2009-08-14 | 일라이 릴리 앤드 캄파니 | 염증 질환 및 암의 치료를 위한 티에노피리미디논 |
| AU2008210455A1 (en) | 2007-01-31 | 2008-08-07 | Vertex Pharmaceuticals Incorporated | 2-aminopyridine derivatives useful as kinase inhibitors |
| EP2139332A4 (en) | 2007-03-28 | 2010-04-21 | Merck Sharp & Dohme | SUBSTITUTED PYRIDO [2,3-D] PYRIMIDIN DERIVATIVES AS CANNABINOID-1 RECEPTOR MODULATORS |
| WO2008150827A1 (en) | 2007-05-29 | 2008-12-11 | Smithkline Beecham Corporation | Naphthyridine, derivatives as p13 kinase inhibitors |
| GB0710528D0 (en) | 2007-06-01 | 2007-07-11 | Glaxo Group Ltd | Novel compounds |
| US9029411B2 (en) * | 2008-01-25 | 2015-05-12 | Millennium Pharmaceuticals, Inc. | Thiophenes and uses thereof |
| US20110201608A1 (en) | 2008-08-05 | 2011-08-18 | Boehringer Ingelheim International Gmbh | Substituted naphthyridines and use thereof as medicines |
| WO2010037765A2 (en) | 2008-10-03 | 2010-04-08 | Merck Serono S.A. | 4-morpholino-pyrido[3,2-d]pyrimidines |
| GB2465405A (en) * | 2008-11-10 | 2010-05-19 | Univ Basel | Triazine, pyrimidine and pyridine analogues and their use in therapy |
| EP2459543B1 (en) | 2009-07-29 | 2017-08-30 | Karus Therapeutics Limited | Benzo[e][1,3]oxazin-4-one derivatives as phosphoinositide 3-kinase inhibitors |
| MX2012002059A (es) | 2009-08-20 | 2012-04-19 | Karus Therapeutics Ltd | Compestos heterociclicos triciclicos como inhibidores de fosfoionositida 3-quinasa. |
| WO2011079231A1 (en) | 2009-12-23 | 2011-06-30 | Gatekeeper Pharmaceutical, Inc. | Compounds that modulate egfr activity and methods for treating or preventing conditions therewith |
| GB201007347D0 (en) | 2010-04-30 | 2010-06-16 | Karus Therapeutics Ltd | Compounds |
| EP4119551A1 (en) | 2011-07-27 | 2023-01-18 | Astrazeneca AB | 2-(2,4,5-substituted-anilino)pyrimidine compounds |
| WO2013017480A1 (en) | 2011-07-29 | 2013-02-07 | Cellzome Limited | Pyrazolo[4,3-c]pyridine derivatives as jak inhibitors |
| GB201204125D0 (en) | 2012-03-08 | 2012-04-25 | Karus Therapeutics Ltd | Compounds |
| WO2014081718A1 (en) | 2012-11-20 | 2014-05-30 | Genentech, Inc. | Aminopyrimidine compounds as inhibitors of t790m containing egfr mutants |
| PT2994465T (pt) | 2013-05-10 | 2018-10-25 | Karus Therapeutics Ltd | Novos inibidores de histona desacetilase |
| CA2914284A1 (en) | 2013-05-30 | 2014-12-04 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| WO2014210354A1 (en) | 2013-06-28 | 2014-12-31 | Genentech, Inc. | Azaindazole compounds as inhibitors of t790m containing egfr mutants |
| ES2818933T3 (es) | 2013-10-10 | 2021-04-14 | Acetylon Pharmaceuticals Inc | Inhibidores de la HDAC en combinación con los inhibidores de la pi3k, para el tratamiento del linfoma no Hodgkin |
| GB201321728D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321730D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321729D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321738D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| GB201402431D0 (en) | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
| GB201514760D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
| GB201514756D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compound and method of use |
| GB201514758D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Formulation |
| GB201514754D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514751D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
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| WO2011021038A1 (en) | 2011-02-24 |
| NZ597983A (en) | 2014-05-30 |
| US20190040079A1 (en) | 2019-02-07 |
| US10501478B2 (en) | 2019-12-10 |
| US20160108057A1 (en) | 2016-04-21 |
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| US9200007B2 (en) | 2015-12-01 |
| US20120178737A1 (en) | 2012-07-12 |
| PL2467387T3 (pl) | 2015-08-31 |
| CN102498115A (zh) | 2012-06-13 |
| IL217903A (en) | 2017-08-31 |
| AU2010286168B2 (en) | 2014-05-15 |
| EP2467387A1 (en) | 2012-06-27 |
| CN102498115B (zh) | 2016-12-07 |
| EP2467387B1 (en) | 2015-01-07 |
| BR112012003955A2 (pt) | 2017-09-26 |
| JP2013502404A (ja) | 2013-01-24 |
| CA2771594C (en) | 2018-05-01 |
| ES2534326T3 (es) | 2015-04-21 |
| CA2771594A1 (en) | 2011-02-24 |
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