ES2834333T3 - Inhibidores pirimidinil de tirosina quinasa - Google Patents
Inhibidores pirimidinil de tirosina quinasa Download PDFInfo
- Publication number
- ES2834333T3 ES2834333T3 ES18171833T ES18171833T ES2834333T3 ES 2834333 T3 ES2834333 T3 ES 2834333T3 ES 18171833 T ES18171833 T ES 18171833T ES 18171833 T ES18171833 T ES 18171833T ES 2834333 T3 ES2834333 T3 ES 2834333T3
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- Prior art keywords
- amino
- compound
- chloro
- oxo
- bipiperidine
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| DK3461821T3 (da) | 2014-10-24 | 2020-08-17 | Bristol Myers Squibb Co | Indolcarboxamidforbindelser, der er brugbar som kinasehæmmere |
| US11174243B2 (en) * | 2016-07-21 | 2021-11-16 | Sunesis Pharmaceuticals, Inc. | Succinate forms and compositions of Bruton's tyrosine kinase inhibitors |
| EP3789040A4 (en) | 2018-04-27 | 2022-03-09 | ONO Pharmaceutical Co., Ltd. | PREVENTIVE AND/OR THERAPEUTIC AGENT FOR AUTOIMMUNE DISEASES WITH A COMPOUND WITH BTK INHIBITING ACTIVITY AS AN INGREDIENT |
| CN117281803A (zh) | 2018-07-31 | 2023-12-26 | 罗索肿瘤学公司 | 喷雾干燥的分散体和制剂 |
| JP2022526713A (ja) | 2019-03-21 | 2022-05-26 | オンクセオ | がんの処置のための、キナーゼ阻害剤と組み合わせたＤｂａｉｔ分子 |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| WO2022140246A1 (en) | 2020-12-21 | 2022-06-30 | Hangzhou Jijing Pharmaceutical Technology Limited | Methods and compounds for targeted autophagy |
| WO2022212893A1 (en) | 2021-04-02 | 2022-10-06 | Biogen Ma Inc. | Combination treatment methods of multiple sclerosis |
| WO2023081709A1 (en) | 2021-11-03 | 2023-05-11 | Viracta Therapeutics, Inc. | Vecabrutinib for the treatment of graft-versus-host disease |
| WO2023081715A1 (en) | 2021-11-03 | 2023-05-11 | Viracta Therapeutics, Inc. | Combination of car t-cell therapy with btk inhibitors and methods of use thereof |
| WO2023110970A1 (en) | 2021-12-14 | 2023-06-22 | Netherlands Translational Research Center Holding B.V | Macrocyclic btk inhibitors |
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Family Cites Families (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1624A (en) * | 1840-06-10 | Cooking-stove | ||
| US4528138A (en) | 1984-06-20 | 1985-07-09 | E. R. Squibb & Sons, Inc. | 16-Keto-17-substituted thia-17-alkyl(or alkenyl or alkynyl) androstenes |
| US4911920A (en) | 1986-07-30 | 1990-03-27 | Alcon Laboratories, Inc. | Sustained release, comfort formulation for glaucoma therapy |
| FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
| JP2594486B2 (ja) | 1991-01-15 | 1997-03-26 | アルコン ラボラトリーズ インコーポレイテッド | 局所的眼薬組成物 |
| US5212162A (en) | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
| US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
| PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| US6919178B2 (en) | 2000-11-21 | 2005-07-19 | Sunesis Pharmaceuticals, Inc. | Extended tethering approach for rapid identification of ligands |
| HUP0300850A2 (hu) | 2000-03-17 | 2003-07-28 | Bristol-Myers Squibb Pharma Company | Gyűrűs béta-aminosav-származékok mint mátrix metalloproteázok és a TNF-alfa inhibitorok és ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk |
| MY137020A (en) | 2000-04-27 | 2008-12-31 | Abbott Lab | Diazabicyclic central nervous system active agents |
| EA006153B1 (ru) | 2000-06-26 | 2005-10-27 | Пфайзер Продактс Инк. | СОЕДИНЕНИЯ ПИРРОЛО[2,3-d]ПИРИМИДИНА В КАЧЕСТВЕ ИММУНОДЕПРЕССАНТОВ |
| PE20020507A1 (es) * | 2000-10-17 | 2002-06-25 | Schering Corp | Compuestos no-imidazoles como antagonistas del receptor histamina h3 |
| WO2003037271A2 (en) * | 2001-10-30 | 2003-05-08 | Millennium Pharmaceuticals,Inc. | Compounds, pharmaceutical compositions and methods of use therefor |
| WO2003037898A1 (en) | 2001-10-31 | 2003-05-08 | Bayer Healthcare Ag | Pyrimido [4,5-b] indole derivatives |
| EP1599468B1 (en) | 2003-01-14 | 2007-10-03 | Arena Pharmaceuticals, Inc. | 1,2,3-trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| ES2344007T3 (es) | 2003-10-14 | 2010-08-16 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Inhibidores proteina quinasa. |
| US20080253960A1 (en) * | 2004-04-01 | 2008-10-16 | The Trustees Of The University Of Pennsylvania Center For Technology Transfer | Lipoprotein-Based Nanoplatforms |
| US8076338B2 (en) | 2004-04-23 | 2011-12-13 | Exelixis, Inc. | Kinase modulators and methods of use |
| FR2870541B1 (fr) | 2004-05-18 | 2006-07-14 | Proskelia Sas | Derives de pyrimidines antigonistes du recepteur de la vitronectine |
| AR050865A1 (es) | 2004-09-09 | 2006-11-29 | Sanofi Aventis | Derivados de 2- morfolino-4-pirimidona |
| MX337817B (es) * | 2004-11-04 | 2011-11-04 | Vertex Pharma | Pirazolo [1,5-a] pirimidinas de utilidad como inhibidores de proteina quinasas. |
| WO2006060461A1 (en) | 2004-12-03 | 2006-06-08 | Schering Corporation | Substituted piperazines as cb1 antagonists |
| ATE543821T1 (de) | 2004-12-28 | 2012-02-15 | Exelixis Inc | Ä1h-pyrazoloä3,4-düpyrimidin-4-ylü-piperidin- oder piperazinverbindungen als serin-threonin- kinasemodulatoren (p70s6k, atk1 und atk2) zur behandlung von immunologischen, entzündlichen und proliferativen erkrankungen |
| WO2006071875A1 (en) | 2004-12-29 | 2006-07-06 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| US7423043B2 (en) * | 2005-02-18 | 2008-09-09 | Lexicon Pharmaceuticals, Inc. | 4-Piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine compounds |
| US20060281700A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using aminopyrimidines kinase modulators |
| US20060281764A1 (en) | 2005-06-10 | 2006-12-14 | Gaul Michael D | Aminopyrimidines as kinase modulators |
| TW200740779A (en) | 2005-07-22 | 2007-11-01 | Mitsubishi Pharma Corp | Intermediate compound for synthesizing pharmaceutical agent and production method thereof |
| MX362412B (es) | 2005-11-01 | 2019-01-15 | Targegen Inc | Inhibidores de biaril meta-pirimidina de cinasas. |
| CN101378807A (zh) * | 2005-12-21 | 2009-03-04 | 先灵公司 | H3拮抗剂/反相激动剂与食欲抑制剂的组合 |
| WO2008005368A2 (en) | 2006-06-30 | 2008-01-10 | Abbott Laboratories | Piperazines as p2x7 antagonists |
| JP2009544732A (ja) | 2006-07-26 | 2009-12-17 | ノバルティス アクチエンゲゼルシャフト | ウンデカプレニルピロホスフェートシンターゼの阻害剤 |
| WO2008012635A2 (en) | 2006-07-26 | 2008-01-31 | Pfizer Products Inc. | Amine derivatives useful as anticancer agents |
| US20100160292A1 (en) | 2006-09-11 | 2010-06-24 | Cgi Pharmaceuticals, Inc | Kinase Inhibitors, and Methods of Using and Identifying Kinase Inhibitors |
| EP2529621B1 (en) * | 2006-09-22 | 2016-10-05 | Pharmacyclics LLC | Inhibitors of bruton's tyrosine kinase |
| WO2008108957A2 (en) * | 2007-03-02 | 2008-09-12 | Schering Corporation | Piperidinyl-piperidine and piperazinyl-piperidine for use in the treatment of diabetes or pain |
| US8188272B2 (en) | 2007-03-21 | 2012-05-29 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| WO2008144253A1 (en) | 2007-05-14 | 2008-11-27 | Irm Llc | Protein kinase inhibitors and methods for using thereof |
| US8093239B2 (en) | 2007-06-01 | 2012-01-10 | Glaxosmithkline Llc | Imidazopyridine kinase inhibitors |
| NZ586916A (en) | 2008-02-05 | 2012-06-29 | Hoffmann La Roche | Novel pyridinones and pyridazinones |
| MX2010011788A (es) | 2008-04-29 | 2011-05-30 | Immunexcite Inc | Composiciones inmunomoduladoras y metodos de uso de las mismas. |
| EP3311818A3 (en) | 2008-07-16 | 2018-07-18 | Pharmacyclics, LLC | Inhibitors of bruton's tyrosine kinase for the treatment of solid tumors |
| WO2010068788A1 (en) * | 2008-12-10 | 2010-06-17 | Cgi Pharmaceuticals, Inc. | Heterocyclic amides as btk inhibitors |
| CN102325753B (zh) * | 2008-12-19 | 2014-09-10 | 百时美施贵宝公司 | 用作激酶抑制剂的咔唑甲酰胺化合物 |
| EP3255047B1 (en) * | 2009-01-06 | 2021-06-30 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone kinase scaffold compounds and uses in treating disorders |
| ES2565205T3 (es) | 2009-05-25 | 2016-04-01 | Sandoz Ag | Método para la producción de ceftobiprol medocaril |
| EP3461824B1 (en) | 2009-09-04 | 2021-08-25 | Biogen MA Inc. | Bruton's tyrosine kinase inhibitors |
| WO2011029043A1 (en) | 2009-09-04 | 2011-03-10 | Biogen Idec Ma Inc. | Heteroaryl btk inhibitors |
| US8685880B2 (en) * | 2010-06-30 | 2014-04-01 | Chevron U.S.A. Inc. | On-site drying of aqueous salt for ionic liquid make-up |
| EP2632898A4 (en) | 2010-10-29 | 2014-04-02 | Biogen Idec Inc | HETEROCYCLIC TYROSINE KINASE HEMMER |
| AR091273A1 (es) * | 2012-06-08 | 2015-01-21 | Biogen Idec Inc | Inhibidores de pirimidinil tirosina quinasa |
| EP2858500A4 (en) | 2012-06-08 | 2016-04-06 | Biogen Ma Inc | BRUTON TYROSINE KINASE HEMMER |
| SI3080103T1 (sl) | 2013-12-11 | 2018-11-30 | Biogen Ma Inc. | Biarilne spojine, ki so uporabne za zdravljenje človeških bolezni na področju onkologije, nevrologije in imunologije |
| WO2015089327A1 (en) | 2013-12-11 | 2015-06-18 | Biogen Idec Ma Inc. | Biaryl compounds useful for the treatment of human diseases in oncology, neurology and immunology |
| US20170298446A1 (en) | 2014-10-03 | 2017-10-19 | Ohio State Innovation Foundation | Biomarkers of bruton tyrosine kinase inhibitor resistance |
| US11174243B2 (en) * | 2016-07-21 | 2021-11-16 | Sunesis Pharmaceuticals, Inc. | Succinate forms and compositions of Bruton's tyrosine kinase inhibitors |
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