TWI569799B - 抑制組成型活性磷酸化ｆｌｔ３激酶的方法 - Google Patents
抑制組成型活性磷酸化ｆｌｔ３激酶的方法 Download PDFInfo
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| JP6407504B2 (ja) * | 2012-09-21 | 2018-10-17 | アログ・ファーマシューティカルズ・インコーポレイテッドＡｒｏｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法 |
| US10835525B2 (en) | 2012-09-26 | 2020-11-17 | Arog Pharmaceuticals, Inc. | Method of inhibiting mutant C-KIT |
| KR20140040594A (ko) | 2012-09-26 | 2014-04-03 | 아로그 파마슈티칼스, 엘엘씨 | 돌연변이체 c-kit의 억제 방법 |
| US11642340B2 (en) | 2012-09-26 | 2023-05-09 | Arog Pharmaceuticals, Inc. | Method of inhibiting mutant C-KIT |
| BR112015016282A2 (en) * | 2013-01-07 | 2017-07-11 | Arog Pharmaceuticals, Inc. | crenolanib for treatment of mutated flt3 proliferative disorders |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| JP7269731B2 (ja) | 2015-03-18 | 2023-05-09 | アルビナス・オペレーションズ・インコーポレイテッド | 標的タンパク質の分解向上のための化合物および方法 |
| CN108137507A (zh) | 2015-07-10 | 2018-06-08 | 阿尔维纳斯股份有限公司 | 基于mdm2的蛋白水解调节剂和相关的使用方法 |
| US12534764B2 (en) | 2016-11-02 | 2026-01-27 | Arog Pharmaceuticals, Inc. | Crenolanib for treating FLT3 mutated proliferative disorders associated mutations |
| RU2019121527A (ru) | 2016-12-23 | 2021-01-15 | Эрвинэс Оперейшнс, Инк. | Химерные молекулы, нацеливающиеся на протеолиз egfr, и связанные с ними способы применения |
| EP3559006A4 (en) | 2016-12-23 | 2021-03-03 | Arvinas Operations, Inc. | COMPOUNDS AND METHODS FOR TARGETED DEGRADATION OF F TAL LIVER KINASE POLYPEPTIDES |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| EP3558994A4 (en) | 2016-12-23 | 2021-05-12 | Arvinas Operations, Inc. | COMPOUNDS AND METHODS FOR TARGETED DEGRADATION OF FAST ACCELERATED FIBROSARCOMA POLYPEPTIDES |
| EP3577109A4 (en) | 2017-01-31 | 2020-11-18 | Arvinas Operations, Inc. | CEREMONY LIGANDS AND BIFUNCTIONAL COMPOUNDS CONTAINING THEM |
| JP2021512153A (ja) | 2018-01-26 | 2021-05-13 | イエール ユニバーシティ | タンパク質分解のイミド系モジュレーターおよび使用方法 |
| CN110840893A (zh) * | 2018-12-13 | 2020-02-28 | 安罗格制药有限责任公司 | 含克莱拉尼的药物组合物及其用途 |
| EP4077309A1 (en) | 2019-12-19 | 2022-10-26 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| WO2022019998A1 (en) | 2020-07-20 | 2022-01-27 | Arog Pharmaceuticals, Inc. | Crystal forms of crenolanib and methods of use thereof |
| CA3186319A1 (en) * | 2020-07-20 | 2022-01-27 | Arog Pharmaceuticals, Inc. | Crystal forms of crenolanib and methods of use thereof |
| EP4204418A1 (en) | 2020-08-28 | 2023-07-05 | Arvinas Operations, Inc. | Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use |
| US20220079934A1 (en) * | 2020-09-17 | 2022-03-17 | Arog Pharmaceuticals, Inc. | Crenolanib for treating pain |
| WO2022090547A1 (en) | 2020-10-30 | 2022-05-05 | Dsm Ip Assets B.V. | Production of carotenoids by fermentation |
| US11969420B2 (en) | 2020-10-30 | 2024-04-30 | Arog Pharmaceuticals, Inc. | Combination therapy of crenolanib and apoptosis pathway agents for the treatment of proliferative disorders |
| CN113683594B (zh) * | 2021-09-07 | 2022-12-27 | 曲靖师范学院 | 一种喹啉-苯并咪唑盐类化合物及其合成方法和应用 |
| EP4584258A1 (en) | 2022-09-07 | 2025-07-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1319966C (zh) * | 2002-08-28 | 2007-06-06 | 辉瑞产品公司 | 可用作抗增殖剂的新苯并咪唑衍生物 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5990146A (en) | 1997-08-20 | 1999-11-23 | Warner-Lambert Company | Benzimidazoles for inhibiting protein tyrosine kinase mediated cellular proliferation |
| JP2001518470A (ja) | 1997-09-26 | 2001-10-16 | メルク エンド カムパニー インコーポレーテッド | 新規な血管形成阻害剤 |
| UA75055C2 (uk) | 1999-11-30 | 2006-03-15 | Пфайзер Продактс Інк. | Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі |
| CA2424689A1 (en) | 2000-10-17 | 2002-04-25 | Merck & Co., Inc. | Orally active salts with tyrosine kinase activity |
| TWI238824B (en) | 2001-05-14 | 2005-09-01 | Novartis Ag | 4-amino-5-phenyl-7-cyclobutyl-pyrrolo[2,3-d]pyrimidine derivatives |
| US7101884B2 (en) | 2001-09-14 | 2006-09-05 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| WO2003024931A1 (en) | 2001-09-14 | 2003-03-27 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TWI259081B (en) | 2001-10-26 | 2006-08-01 | Sugen Inc | Treatment of acute myeloid leukemia with indolinone compounds |
| IL161156A0 (en) | 2001-10-30 | 2004-08-31 | Novartis Ag | Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity |
| WO2003057690A1 (en) | 2001-12-27 | 2003-07-17 | Theravance, Inc. | Indolinone derivatives useful as protein kinase inhibitors |
| TW200406374A (en) | 2002-05-29 | 2004-05-01 | Novartis Ag | Diaryl urea derivatives useful for the treatment of protein kinase dependent diseases |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| CA2495386C (en) | 2002-08-14 | 2011-06-21 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors and uses thereof |
| CA2496164C (en) | 2002-08-23 | 2010-11-09 | Chiron Corporation | Benzimidazole quinolinones and uses thereof |
| EP1566379A4 (en) | 2002-10-29 | 2005-11-09 | Kirin Brewery | CHINOLINE DERIVATIVES AND CHINAZOLINE DERIVATIVES AS INHIBITORS OF FLT3 AUTOPHOSPHORYLATION AND THE MEDICAL COMPOSITIONS CONTAINING THEREOF |
| CA2501932C (en) | 2002-11-13 | 2014-03-11 | Chiron Corporation | Use of benzimidazole quinolinones for treating cancer |
| AR042052A1 (es) | 2002-11-15 | 2005-06-08 | Vertex Pharma | Diaminotriazoles utiles como inhibidores de proteinquinasas |
| ATE425160T1 (de) | 2002-12-18 | 2009-03-15 | Vertex Pharma | Benzisoxazolderivate, die sich als inhibitoren von proteinkinasen eigen |
| WO2004113322A1 (en) | 2003-06-24 | 2004-12-29 | Pfizer Products Inc. | Processes for the preparation of 1-[(benzoimidazole-1yl) quinolin-8-yl] piperidin-4-ylamine derivatives |
| WO2006038111A1 (en) * | 2004-10-07 | 2006-04-13 | Pfizer Products Inc. | Benzoimidazole derivatives useful as antiproliferative agents |
| JP2013505230A (ja) * | 2009-09-17 | 2013-02-14 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッド | 酸化ストレス関連障害を処置するためのペプチド |
| WO2012052757A1 (en) * | 2010-10-20 | 2012-04-26 | Astrazeneca Ab | Tumour phenotype patient selection method |
| RU2568258C2 (ru) | 2011-02-28 | 2015-11-20 | Саншайн Лейк Фарма Ко., Лтд | Замещенные соединения хинолина и способы их использования |
| JP6407504B2 (ja) | 2012-09-21 | 2018-10-17 | アログ・ファーマシューティカルズ・インコーポレイテッドＡｒｏｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法 |
| KR20140040594A (ko) | 2012-09-26 | 2014-04-03 | 아로그 파마슈티칼스, 엘엘씨 | 돌연변이체 c-kit의 억제 방법 |
| BR112015016282A2 (en) | 2013-01-07 | 2017-07-11 | Arog Pharmaceuticals, Inc. | crenolanib for treatment of mutated flt3 proliferative disorders |
| US11969420B2 (en) * | 2020-10-30 | 2024-04-30 | Arog Pharmaceuticals, Inc. | Combination therapy of crenolanib and apoptosis pathway agents for the treatment of proliferative disorders |
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Patent Citations (1)
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|---|---|---|---|---|
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| CA2812245A1 (en) | 2014-03-21 |
| JP2017132772A (ja) | 2017-08-03 |
| CN103655564B (zh) | 2019-04-02 |
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