JP5400388B2 - キナーゼインヒビターおよびその利用 - Google Patents
キナーゼインヒビターおよびその利用 Download PDFInfo
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- JP5400388B2 JP5400388B2 JP2008545992A JP2008545992A JP5400388B2 JP 5400388 B2 JP5400388 B2 JP 5400388B2 JP 2008545992 A JP2008545992 A JP 2008545992A JP 2008545992 A JP2008545992 A JP 2008545992A JP 5400388 B2 JP5400388 B2 JP 5400388B2
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- Prior art keywords
- exo
- hept
- diamine
- racemic
- 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.)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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| US75139305P | 2005-12-15 | 2005-12-15 | |
| US60/751,393 | 2005-12-15 | ||
| PCT/US2006/062162 WO2007070872A1 (en) | 2005-12-15 | 2006-12-15 | Kinase inhibitors and their uses |
Publications (3)
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| JP2009519979A JP2009519979A (ja) | 2009-05-21 |
| JP2009519979A5 JP2009519979A5 (https=) | 2010-02-04 |
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| WO (1) | WO2007070872A1 (https=) |
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| MX2007013595A (es) | 2005-05-04 | 2008-01-24 | Renovis Inc | Compuestos heterociclicos fusionados y composiciones y usos de estos. |
| JP5400388B2 (ja) * | 2005-12-15 | 2014-01-29 | ライジェル ファーマシューティカルズ， インコーポレイテッド | キナーゼインヒビターおよびその利用 |
| TW200808360A (en) * | 2006-04-13 | 2008-02-16 | Alcon Mfg Ltd | RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions |
| WO2008045978A1 (en) * | 2006-10-10 | 2008-04-17 | Rigel Pharmaceuticals, Inc. | Pinane-substituted pyrimidinediamine derivatives useful as axl inhibitors |
| EP2311807B1 (en) | 2006-12-08 | 2015-11-11 | Novartis AG | Compounds and composition as protein kinase inhibitors |
| US20100298557A1 (en) | 2006-12-28 | 2010-11-25 | Taisho Pharmaceutical Co., Ltd | Pyrazolopyrimidine compound |
| WO2009005813A1 (en) * | 2007-07-02 | 2009-01-08 | Wyeth | Modulators of axl for use in treating bone disorders |
| US7981903B2 (en) * | 2007-08-08 | 2011-07-19 | Glaxosmithkline Llc | 2-[2-{phenylamino}-1H-pyrrolo[2,3-D]pyrimidin-4-yl)amino] benzamide derivatives as IGF-1R inhibitors for the treatment of cancer |
| WO2009032703A1 (en) * | 2007-08-28 | 2009-03-12 | Irm Llc | 2- (het) arylamino-6-aminopyridine derivatives and fused forms thereof as anaplastic lymphoma kinase inhibitors |
| WO2009029682A1 (en) * | 2007-08-28 | 2009-03-05 | Rigel Pharmaceuticals, Inc. | Combination therapy with syk kinase inhibitor |
| EP2217716A4 (en) | 2007-11-09 | 2011-02-09 | Salk Inst For Biological Studi | USE OF TAM RECEPTOR INHIBITORS AS ANTIMICROBIAL AGENTS |
| EP3109249A1 (en) | 2007-11-15 | 2016-12-28 | YM BioSciences Australia Pty Ltd | N-containing heterocyclic compounds |
| TW200942537A (en) * | 2008-02-01 | 2009-10-16 | Irm Llc | Compounds and compositions as kinase inhibitors |
| MX2010011463A (es) | 2008-04-16 | 2011-06-03 | Portola Pharm Inc | 2,6-diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o jak quinasas. |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| NZ588830A (en) * | 2008-04-22 | 2012-11-30 | Portola Pharm Inc | Inhibitors of protein kinases |
| BRPI0909945A2 (pt) | 2008-06-20 | 2015-07-28 | Genentech Inc | "composto, composição farmacêutica, método para tratar ou atenuar a gravidade de uma doença ou condição responsiva à inibição da atividade jak2 quinase em um paciente, kit para o tratamento de uma doença ou distúrbio responsivo à inibição da jak quinase" |
| EP2288260A4 (en) | 2008-06-20 | 2013-10-23 | Genentech Inc | TRIAZOLOPYRIDINE-JAK HEMMER COMPOUNDS AND METHOD |
| SG172997A1 (en) | 2009-01-16 | 2011-08-29 | Rigel Pharmaceuticals Inc | Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer |
| US20100204221A1 (en) * | 2009-02-09 | 2010-08-12 | Hariprasad Vankayalapati | Pyrrolopyrimidinyl axl kinase inhibitors |
| TW201100427A (en) | 2009-03-31 | 2011-01-01 | Arqule Inc | Substituted heterocyclic compounds |
| CN105037364B (zh) * | 2009-04-03 | 2018-04-27 | 维拉斯通股份有限公司 | 作为激酶抑制剂的嘧啶取代的嘌呤化合物 |
| ES2500643T3 (es) | 2009-04-03 | 2014-09-30 | Verastem, Inc. | Compuestos de purina sustituidos con pirimidina como inhibidores de las cinasas |
| TW201105669A (en) * | 2009-07-30 | 2011-02-16 | Irm Llc | Compounds and compositions as Syk kinase inhibitors |
| JP2013501002A (ja) | 2009-07-30 | 2013-01-10 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｓｙｋキナーゼ阻害剤としての化合物および組成物 |
| CN102471338B (zh) | 2009-08-07 | 2014-07-02 | 默克专利有限公司 | 氮杂杂环化合物 |
| KR101094446B1 (ko) | 2009-11-19 | 2011-12-15 | 한국과학기술연구원 | 단백질 키나아제 저해활성을 가지는 2,4,7-치환된 티에노［3,2-ｄ］피리미딘 화합물 |
| SG181857A1 (en) * | 2009-12-23 | 2012-07-30 | Takeda Pharmaceutical | Fused heteroaromatic pyrrolidinones as syk inhibitors |
| EP2441755A1 (en) * | 2010-09-30 | 2012-04-18 | Almirall, S.A. | Pyridine- and isoquinoline-derivatives as Syk and JAK kinase inhibitors |
| FR2967854A1 (fr) * | 2010-11-19 | 2012-05-25 | France Telecom | Procede de communication dans un reseau cooperatif |
| EP2489663A1 (en) | 2011-02-16 | 2012-08-22 | Almirall, S.A. | Compounds as syk kinase inhibitors |
| MX343517B (es) | 2011-03-10 | 2016-11-07 | Rigel Pharmaceuticals Inc | 2,4 pirimidinadiaminas sustituidas para su uso en lupus discoide. |
| EP2707357B1 (en) | 2011-05-10 | 2017-01-18 | Merck Sharp & Dohme Corp. | Pyridyl aminopyridines as syk inhibitors |
| US9145391B2 (en) | 2011-05-10 | 2015-09-29 | Merck Sharp & Dohme Corp. | Bipyridylaminopyridines as Syk inhibitors |
| MX2013013090A (es) | 2011-05-10 | 2013-12-16 | Merck Sharp & Dohme | Aminopirimidinas como inhibidores de tirosina cinaza del bazo. |
| JP6026525B2 (ja) * | 2011-06-22 | 2016-11-16 | 武田薬品工業株式会社 | 置換６−アザ−イソインドリン−１−オン誘導体 |
| WO2013052391A1 (en) | 2011-10-05 | 2013-04-11 | Merck Sharp & Dohme Corp. | PHENYL CARBOXAMIDE-CONTAINING SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| EP2763976B1 (en) | 2011-10-05 | 2016-05-18 | Merck Sharp & Dohme Corp. | 2-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
| WO2013052393A1 (en) | 2011-10-05 | 2013-04-11 | Merck Sharp & Dohme Corp. | 3-PYRIDYL CARBOXAMIDE-CONTAINING SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| CA3094793A1 (en) | 2011-11-23 | 2013-05-30 | Portola Pharmaceuticals, Inc. | Pyrazine kinase inhibitors |
| RS55728B1 (sr) | 2012-01-31 | 2017-07-31 | Daiichi Sankyo Co Ltd | Derivat piridona |
| WO2013162061A1 (ja) * | 2012-04-26 | 2013-10-31 | 第一三共株式会社 | 二環性ピリミジン化合物 |
| US9487504B2 (en) | 2012-06-20 | 2016-11-08 | Merck Sharp & Dohme Corp. | Imidazolyl analogs as syk inhibitors |
| EP2863914B1 (en) | 2012-06-20 | 2018-10-03 | Merck Sharp & Dohme Corp. | Pyrazolyl derivatives as syk inhibitors |
| EP2863915B1 (en) | 2012-06-22 | 2017-12-06 | Merck Sharp & Dohme Corp. | SUBSTITUTED DIAZINE AND TRIAZINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| EP2863916B1 (en) | 2012-06-22 | 2018-07-18 | Merck Sharp & Dohme Corp. | Substituted pyridine spleen tyrosine kinase (syk) inhibitors |
| WO2014013014A1 (en) | 2012-07-18 | 2014-01-23 | Fundació Privada Centre De Regulació Genòmica (Crg) | Jak inhibitors for activation of epidermal stem cell populations |
| CA2879542A1 (en) | 2012-07-25 | 2014-01-30 | Salk Institute For Biological Studies | Regulating the interaction between tam ligands and lipid membranes with exposed phosphatidylserine |
| EP2884982B1 (en) | 2012-08-20 | 2017-09-20 | Merck Sharp & Dohme Corp. | SUBSTITUTED PHENYL SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| EP2895172B1 (en) | 2012-09-12 | 2019-02-06 | Rigel Pharmaceuticals, Inc. | Treatment for vitiligo |
| EP2900665B1 (en) | 2012-09-28 | 2018-01-03 | Merck Sharp & Dohme Corp. | Triazolyl derivatives as syk inhibitors |
| WO2014093191A1 (en) | 2012-12-12 | 2014-06-19 | Merck Sharp & Dohme Corp. | AMINO-PYRIMIDINE-CONTAINING SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| EP2934525B1 (en) | 2012-12-21 | 2019-05-08 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors |
| EP2988744A4 (en) | 2013-04-26 | 2016-11-02 | Merck Sharp & Dohme | THIAZOLSUBSTITUTED AMINOHETEROARYLE AS MILZTYROSINKINASE INHIBITOR |
| EP2988749B1 (en) | 2013-04-26 | 2019-08-14 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyrimidines as spleen tyrosine kinase inhibitors |
| EP3083560B1 (en) | 2013-12-20 | 2021-10-27 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| US9822107B2 (en) | 2013-12-20 | 2017-11-21 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| US9783531B2 (en) | 2013-12-20 | 2017-10-10 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| WO2015138273A1 (en) | 2014-03-13 | 2015-09-17 | Merck Sharp & Dohme Corp. | 2-pyrazine carboxamides as spleen tyrosine kinase inhibitors |
| TWI690525B (zh) | 2014-07-07 | 2020-04-11 | 日商第一三共股份有限公司 | 具有四氫吡喃基甲基之吡啶酮衍生物及其用途 |
| US10611765B2 (en) | 2014-11-06 | 2020-04-07 | Ohio State Innovation Foundation | Pyrrolopyrimidine derivatives as Mps1/TTK kinase inhibitors |
| MY199935A (en) * | 2014-12-18 | 2023-11-29 | Wells Therapeutics Inc | Solid state forms of fused heteroaromatic pyrrolidinones |
| US9840503B2 (en) | 2015-05-11 | 2017-12-12 | Incyte Corporation | Heterocyclic compounds and uses thereof |
| WO2017027717A1 (en) | 2015-08-12 | 2017-02-16 | Incyte Corporation | Bicyclic fused pyrimidine compounds as tam inhibitors |
| US10053465B2 (en) | 2015-08-26 | 2018-08-21 | Incyte Corporation | Pyrrolopyrimidine derivatives as TAM inhibitors |
| WO2017146236A1 (ja) | 2016-02-26 | 2017-08-31 | 小野薬品工業株式会社 | Ａｘｌ阻害剤と免疫チェックポイント阻害剤とを組み合わせて投与することを特徴とする癌治療のための医薬 |
| MD3436461T2 (ro) | 2016-03-28 | 2024-05-31 | Incyte Corp | Compuși pirolotriazină ca inhibitori TAM |
| CN107698603B (zh) | 2016-08-09 | 2022-04-08 | 南京红云生物科技有限公司 | 噻吩并嘧啶类化合物、其制备方法、药用组合物及其应用 |
| WO2018041989A1 (en) | 2016-09-02 | 2018-03-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for diagnosing and treating refractory celiac disease type 2 |
| JP7156287B2 (ja) | 2017-08-23 | 2022-10-19 | 小野薬品工業株式会社 | Ａｘｌ阻害剤を有効成分として含むがん治療剤 |
| SI3687996T1 (sl) | 2017-09-27 | 2022-04-29 | Incyte Corporation | Soli pirolotriazinskih derivatov, ki so uporabne kot zaviralci TAM |
| EP3695839A4 (en) | 2017-10-13 | 2021-07-14 | ONO Pharmaceutical Co., Ltd. | THERAPEUTIC AGENT WITH AXL INHIBITOR AS AN ACTIVE INGREDIENT FOR SOLID TUMORS |
| EP3814354B1 (en) * | 2018-06-22 | 2023-11-08 | The Royal Institution for the Advancement of Learning / McGill University | Purine compounds and method for the treatment of cancer |
| MD3813800T2 (ro) | 2018-06-29 | 2025-10-31 | Incyte Corp | Formulări de inhibitor al AXL/MER |
| JP2022527972A (ja) | 2019-04-02 | 2022-06-07 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 前悪性病変を有する患者において癌を予測及び予防する方法 |
| US20220202820A1 (en) | 2019-04-16 | 2022-06-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of jak inhibitors for the treatment of painful conditions involving nav1.7 channels |
| EP4114401A1 (en) | 2020-03-06 | 2023-01-11 | Incyte Corporation | Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors |
| EP4526469A1 (en) | 2022-05-16 | 2025-03-26 | Institut National de la Santé et de la Recherche Médicale | Methods for assessing the exhaustion of hematopoietic stems cells induced by chronic inflammation |
| WO2024054793A1 (en) | 2022-09-09 | 2024-03-14 | University Of Rochester | Inhibition of efferocytosis as a treatment to prevent bone loss and increase bone density and strength |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9611157A (pt) * | 1995-11-01 | 1999-03-30 | Novartis Ag | Derivados de purina e processos para sua preparação |
| WO1997020822A1 (en) * | 1995-12-01 | 1997-06-12 | Novartis Ag | Quinazolin-2,4-diazirines as npy receptor antagonist |
| AU7692696A (en) * | 1995-12-01 | 1997-06-27 | Novartis Ag | Heteroaryl derivatives |
| GB9903762D0 (en) * | 1999-02-18 | 1999-04-14 | Novartis Ag | Organic compounds |
| GB9918035D0 (en) | 1999-07-30 | 1999-09-29 | Novartis Ag | Organic compounds |
| EP1230225A2 (en) | 1999-11-01 | 2002-08-14 | Eli Lilly And Company | Pharmaceutically active 4-substituted pyrimidine derivatives |
| FR2818642B1 (fr) * | 2000-12-26 | 2005-07-15 | Hoechst Marion Roussel Inc | Nouveaux derives de la purine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilistion |
| PE20030008A1 (es) * | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| JP2005509612A (ja) * | 2001-10-12 | 2005-04-14 | アイアールエム エルエルシー | 置換プリンの合成方法 |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| US6897307B2 (en) * | 2002-03-28 | 2005-05-24 | Novartis Ag | Process for preparing 2,6-diaminopurine derivatives |
| US7129239B2 (en) | 2002-10-28 | 2006-10-31 | Pfizer Inc. | Purine compounds and uses thereof |
| AU2003291310A1 (en) * | 2002-11-06 | 2004-06-03 | Bristol-Myers Squibb Company | Fused heterocyclic compounds and use thereof |
| EP1643936B1 (en) | 2003-07-14 | 2010-08-11 | University of Limerick | A vascular graft |
| EP1656378A4 (en) * | 2003-08-15 | 2011-05-11 | Irm Llc | COMPOUNDS AND COMPOSITIONS INHIBITING TYROSINE KINASE RECEPTOR ACTIVITY |
| US7951592B2 (en) * | 2003-11-10 | 2011-05-31 | The Scripps Research Institute | Compositions and methods for inducing cell dedifferentiation |
| GB0327319D0 (en) | 2003-11-24 | 2003-12-24 | Pfizer Ltd | Novel pharmaceuticals |
| ATE387446T1 (de) * | 2003-12-16 | 2008-03-15 | Pfizer Prod Inc | Pyrido(2,3-d)pyrimidin-2,4-diamine als pde-2- inhibitoren |
| GB0407723D0 (en) * | 2004-04-05 | 2004-05-12 | Novartis Ag | Organic compounds |
| EP1763514A2 (en) | 2004-05-18 | 2007-03-21 | Rigel Pharmaceuticals, Inc. | Cycloalkyl substituted pyrimidinediamine compounds and their uses |
| CN101031551A (zh) * | 2004-07-06 | 2007-09-05 | 安吉永生物制药公司 | 针对癌症治疗的肝细胞生长因子/c－met活性的喹唑啉调节剂 |
| ATE421996T1 (de) | 2004-11-15 | 2009-02-15 | Rigel Pharmaceuticals Inc | Verfahren zur herstellung optisch aktiver n- carbamat-geschützter beta-lactame durch optische auflösung unter verwendung einer candida antarctica lipase |
| GB2420559B (en) | 2004-11-15 | 2008-08-06 | Rigel Pharmaceuticals Inc | Stereoisomerically enriched 3-aminocarbonyl bicycloheptene pyrimidinediamine compounds and their uses |
| WO2006105056A2 (en) * | 2005-03-28 | 2006-10-05 | Fmc Corporation | Insecticidal 2,4-diaminoquinazolines and related derivatives |
| CN100526315C (zh) | 2005-06-16 | 2009-08-12 | 浙江医药股份有限公司新昌制药厂 | N2-喹啉或异喹啉取代的嘌呤衍生物及其制备方法和其用途 |
| WO2007042298A1 (en) * | 2005-10-13 | 2007-04-19 | Glaxo Group Limited | Pyrrolopyrimidine derivatives as syk inhibitors |
| JP5400388B2 (ja) * | 2005-12-15 | 2014-01-29 | ライジェル ファーマシューティカルズ， インコーポレイテッド | キナーゼインヒビターおよびその利用 |
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| US9096542B2 (en) | 2015-08-04 |
| US20120015937A1 (en) | 2012-01-19 |
| EP1960372A1 (en) | 2008-08-27 |
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