JP2013510886A - キナーゼ阻害剤 - Google Patents
キナーゼ阻害剤 Download PDFInfo
- Publication number
- JP2013510886A JP2013510886A JP2012539076A JP2012539076A JP2013510886A JP 2013510886 A JP2013510886 A JP 2013510886A JP 2012539076 A JP2012539076 A JP 2012539076A JP 2012539076 A JP2012539076 A JP 2012539076A JP 2013510886 A JP2013510886 A JP 2013510886A
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- Prior art keywords
- substituted
- unsubstituted
- heteroaryl
- alkyl
- heterocycloalkyl
- Prior art date
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| US61/330,271 | 2010-04-30 | ||
| PCT/US2010/056890 WO2011060440A2 (en) | 2009-11-16 | 2010-11-16 | Kinase inhibitors |
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| CA (1) | CA2781056A1 (enExample) |
| MX (1) | MX2012005678A (enExample) |
| WO (1) | WO2011060440A2 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2710005T1 (sl) | 2011-05-17 | 2017-03-31 | Principia Biopharma Inc. | Zaviralci tirozinske kinaze |
| US9376438B2 (en) | 2011-05-17 | 2016-06-28 | Principia Biopharma, Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
| BR112013029508B1 (pt) * | 2011-05-17 | 2022-05-03 | Principia Biopharma, Inc. | Composto, composição farmacêutica, e, uso do referido composto |
| MX368112B (es) | 2012-06-18 | 2019-09-18 | Principia Biopharma Inc | Pirrolo- o pirazolopirimidinas covalentes reversibles utiles para el tratamiento del cancer y de enfermedades autoinmunitarias. |
| JP2015526520A (ja) | 2012-08-31 | 2015-09-10 | プリンシピア バイオファーマ インコーポレイテッド | Itk阻害剤としてのベンズイミダゾール誘導体 |
| RS58956B1 (sr) | 2012-09-10 | 2019-08-30 | Principia Biopharma Inc | Jedinjenja pirazolopirimidina kao inhibitori kinaze |
| WO2014093230A2 (en) | 2012-12-10 | 2014-06-19 | Merck Patent Gmbh | Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity |
| US8957080B2 (en) | 2013-04-09 | 2015-02-17 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
| EA033900B1 (ru) | 2014-02-21 | 2019-12-06 | Принсипиа Биофарма Инк. | СОЛЕВЫЕ И АМОРФНЫЕ ФОРМЫ 2-[(3R)-3-[4-АМИНО-3-(2-ФТОР-4-ФЕНОКСИФЕНИЛ)ПИРАЗОЛО[3,4-d]ПИРИМИДИН-1-ИЛ]ПИПЕРИДИН-1-КАРБОНИЛ]-4-МЕТИЛ-4-[4-(ОКСЕТАН-3-ИЛ)ПИПЕРАЗИН-1-ИЛ]ПЕНТ-2-ЕННИТРИЛА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ ПУЗЫРЧАТКИ ОБЫКНОВЕННОЙ И ПУЗЫРЧАТКИ ЛИСТОВИДНОЙ С ИХ ПРИМЕНЕНИЕМ |
| PL3166608T3 (pl) | 2014-07-07 | 2019-07-31 | Jiangsu Hengrui Medicine Co., Ltd. | Związki aminopirydazynonowe jako inhibitory kinaz białkowych |
| CA2970723C (en) | 2014-12-18 | 2023-09-05 | Principia Biopharma Inc. | Treatment of pemphigus |
| EP3313839A1 (en) | 2015-06-24 | 2018-05-02 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
| WO2017118277A1 (zh) * | 2016-01-05 | 2017-07-13 | 江苏恒瑞医药股份有限公司 | 一种btk激酶抑制剂的结晶形式及其制备方法 |
| CN106939002B (zh) * | 2016-01-05 | 2019-09-24 | 江苏恒瑞医药股份有限公司 | 一种btk激酶抑制剂的结晶形式及其制备方法 |
| SG11201811255WA (en) | 2016-06-29 | 2019-01-30 | Principia Biopharma Inc | Modified release formulations of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
| JOP20180094A1 (ar) | 2017-10-18 | 2019-04-18 | Hk Inno N Corp | مركب حلقي غير متجانس كمثبط بروتين كيناز |
| KR102195348B1 (ko) | 2018-11-15 | 2020-12-24 | 에이치케이이노엔 주식회사 | 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 |
| CN115209899A (zh) | 2019-10-14 | 2022-10-18 | 普林斯匹亚生物制药公司 | 通过施用(R)-2-[3-[4-氨基-3-(2-氟-4-苯氧基-苯基)吡唑并[3,4-d]嘧啶-1-基]哌啶-1-羰基]-4-甲基-4-[4-(氧杂环丁-3-基)哌嗪-1-基]戊-2-烯腈治疗免疫性血小板减少症的方法 |
| MX2022009009A (es) | 2020-01-22 | 2022-08-15 | Principia Biopharma Inc | Formas cristalinas de 2-[3-[4-amino-3-(2-fluoro-4-fenoxi-fenil)-1h -pirazolo[3,4-d]pirimidin-1-il]piperidin-1-carbonil]-4-metil-4-[4 -(oxetan-3-il)piperazin-1-il]pent-2-enonitrilo. |
| CN111205232B (zh) * | 2020-02-26 | 2022-07-01 | 浙江天宇药业股份有限公司 | 一种替格瑞洛中间体的合成方法 |
| TW202307005A (zh) | 2021-05-28 | 2023-02-16 | 美商邊際分析公司 | 以核醣體蛋白質S6激酶α-1 (RSK1)及核醣體蛋白質S6激酶α-3 (RSK2)之調節劑治療神經病症之方法 |
| CN116332996B (zh) * | 2023-05-04 | 2025-04-01 | 南京颐媛生物医学研究院有限公司 | L-呋喃核糖型抗冠状病毒化合物及其制备方法和应用 |
| CN116410228B (zh) * | 2023-05-04 | 2025-10-31 | 南京颐媛生物医学研究院有限公司 | 一种抗冠状病毒核苷类化合物的制备方法及其应用 |
| CN116284135B (zh) * | 2023-05-04 | 2025-03-21 | 南京颐媛生物医学研究院有限公司 | 抗冠状病毒核苷类化合物的制备方法及其应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04506081A (ja) * | 1990-02-28 | 1992-10-22 | フアルミタリア・カルロ・エルバ・エツセ・エルレ・エルレ | 新規なアリールエテニレン及びヘテロアリールエテニレン誘導体及びその製法 |
| JPH07504208A (ja) * | 1992-12-23 | 1995-05-11 | フアルミタリア・カルロ・エルバ・エツセ・エルレ・エルレ | ビニレン−アザインドール誘導体及びその製造方法 |
| JPH08511562A (ja) * | 1994-03-28 | 1996-12-03 | フアルマシア・エツセ・ピー・アー | N−置換β−アリール−及びβ−ヘテロアリール−α−シアノアクリルアミド誘導体及びそれらの製造方法 |
| WO1999043673A1 (en) * | 1998-02-26 | 1999-09-02 | Zenyaku Kogyo Kabushiki Kaisha | 1-azaindolizine derivatives |
| US6331555B1 (en) * | 1995-06-01 | 2001-12-18 | University Of California | Treatment of platelet derived growth factor related disorders such as cancers |
| WO2008079460A2 (en) * | 2006-09-05 | 2008-07-03 | Emory University | Tyrosine kinase inhibitors for prevention or treatment of infection |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444770A (en) * | 1980-05-29 | 1984-04-24 | Bayer Aktiengesellschaft | New imidazoazole-alkenoic acid amide compounds, intermediate products for their production, their production, and their medicinal use |
| DE3216416A1 (de) * | 1982-05-03 | 1983-11-03 | Bayer Ag, 5090 Leverkusen | Heteroarylthiovinyl-verbindungen, ein verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel |
| US4911920A (en) | 1986-07-30 | 1990-03-27 | Alcon Laboratories, Inc. | Sustained release, comfort formulation for glaucoma therapy |
| DE3502264A1 (de) * | 1985-01-24 | 1986-07-24 | Bayer Ag, 5090 Leverkusen | Imidazoalkensaeurederivate, ein verfahren zu ihrer herstellung und ihre verwendung fuer die herstellung pharmazeutischer wirkstoffe |
| FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
| DE68921643T2 (de) * | 1988-12-26 | 1995-07-06 | Zenyaku Kogyo Kk | 1-azaindolizin-derivat, zwischenprodukt dazu und antiallergisches mittel, enthaltend ein 1-azaindolizin-derivat. |
| 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 |
| JPH05301838A (ja) * | 1991-10-15 | 1993-11-16 | Mitsubishi Kasei Corp | スチレン誘導体 |
| US5792771A (en) * | 1992-11-13 | 1998-08-11 | Sugen, Inc. | Quinazoline compounds and compositions thereof for the treatment of disease |
| WO1995024190A2 (en) * | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
| GB9412719D0 (en) * | 1994-06-24 | 1994-08-17 | Erba Carlo Spa | Substituted azaindolylidene compounds and process for their preparation |
| ES2295930T3 (es) * | 2003-08-01 | 2008-04-16 | Chugai Seiyaku Kabushiki Kaisha | Compuestos de cianoamida utiles como inhibidores de malonil-coa descarboxilasa. |
| US7807719B2 (en) * | 2004-09-14 | 2010-10-05 | Chaim Roifman | Compounds useful for modulating abnormal cell proliferation |
| US7947707B2 (en) * | 2005-10-07 | 2011-05-24 | Kissei Pharmaceutical Co., Ltd. | Nitrogenated heterocyclic compound and pharmaceutical composition comprising the same |
| BRPI0709916B8 (pt) * | 2006-03-31 | 2021-05-25 | Univ Texas | drogas anticâncer associadas ao ácido caféico biodisponível por via oral e uso das referidas drogas |
| US7645748B2 (en) | 2006-04-03 | 2010-01-12 | Forbes Medi-Tech Inc. | Sterol/stanol phosphorylnitroderivatives and use thereof |
| WO2008005954A2 (en) * | 2006-06-30 | 2008-01-10 | The Board Of Regents Of The University Of Texas System | Tryphostin-analogs for the treatment of cell proliferative diseases |
| US20100113520A1 (en) | 2008-11-05 | 2010-05-06 | Principia Biopharma, Inc. | Kinase knockdown via electrophilically enhanced inhibitors |
| US20120028981A1 (en) | 2008-11-05 | 2012-02-02 | Principia Biopharma Inc. | Kinase Knockdown Via Electrophilically Enhanced Inhibitors |
| US8426428B2 (en) | 2008-12-05 | 2013-04-23 | Principia Biopharma, Inc. | EGFR kinase knockdown via electrophilically enhanced inhibitors |
-
2010
- 2010-11-16 MX MX2012005678A patent/MX2012005678A/es not_active Application Discontinuation
- 2010-11-16 US US13/510,272 patent/US20130035325A1/en not_active Abandoned
- 2010-11-16 CN CN2010800615701A patent/CN102711765A/zh active Pending
- 2010-11-16 EP EP10830919.6A patent/EP2558099A4/en not_active Withdrawn
- 2010-11-16 JP JP2012539076A patent/JP2013510886A/ja active Pending
- 2010-11-16 WO PCT/US2010/056890 patent/WO2011060440A2/en not_active Ceased
- 2010-11-16 CA CA2781056A patent/CA2781056A1/en not_active Abandoned
- 2010-11-16 AU AU2010319964A patent/AU2010319964A1/en not_active Abandoned
- 2010-11-16 BR BR112012011528A patent/BR112012011528A2/pt not_active IP Right Cessation
-
2014
- 2014-08-18 US US14/462,158 patent/US9505766B2/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04506081A (ja) * | 1990-02-28 | 1992-10-22 | フアルミタリア・カルロ・エルバ・エツセ・エルレ・エルレ | 新規なアリールエテニレン及びヘテロアリールエテニレン誘導体及びその製法 |
| JPH07504208A (ja) * | 1992-12-23 | 1995-05-11 | フアルミタリア・カルロ・エルバ・エツセ・エルレ・エルレ | ビニレン−アザインドール誘導体及びその製造方法 |
| JPH08511562A (ja) * | 1994-03-28 | 1996-12-03 | フアルマシア・エツセ・ピー・アー | N−置換β−アリール−及びβ−ヘテロアリール−α−シアノアクリルアミド誘導体及びそれらの製造方法 |
| US6331555B1 (en) * | 1995-06-01 | 2001-12-18 | University Of California | Treatment of platelet derived growth factor related disorders such as cancers |
| WO1999043673A1 (en) * | 1998-02-26 | 1999-09-02 | Zenyaku Kogyo Kabushiki Kaisha | 1-azaindolizine derivatives |
| WO2008079460A2 (en) * | 2006-09-05 | 2008-07-03 | Emory University | Tyrosine kinase inhibitors for prevention or treatment of infection |
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| AU2010319964A1 (en) | 2012-06-07 |
| US9505766B2 (en) | 2016-11-29 |
| CN102711765A (zh) | 2012-10-03 |
| US20130035325A1 (en) | 2013-02-07 |
| WO2011060440A2 (en) | 2011-05-19 |
| WO2011060440A3 (en) | 2011-11-03 |
| EP2558099A2 (en) | 2013-02-20 |
| EP2558099A4 (en) | 2013-07-17 |
| US20150045343A1 (en) | 2015-02-12 |
| MX2012005678A (es) | 2012-09-07 |
| BR112012011528A2 (pt) | 2019-09-24 |
| AU2010319964A2 (en) | 2012-08-02 |
| CA2781056A1 (en) | 2011-05-19 |
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