CA2813607C - Substituted pyridazine carboxamide compounds - Google Patents
Substituted pyridazine carboxamide compounds Download PDFInfo
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- CA2813607C CA2813607C CA2813607A CA2813607A CA2813607C CA 2813607 C CA2813607 C CA 2813607C CA 2813607 A CA2813607 A CA 2813607A CA 2813607 A CA2813607 A CA 2813607A CA 2813607 C CA2813607 C CA 2813607C
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- disease
- compound
- alkyl
- dichloro
- cycloalkyl
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Classifications
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Landscapes
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| US39142310P | 2010-10-08 | 2010-10-08 | |
| US61/391,423 | 2010-10-08 | ||
| PCT/US2011/055428 WO2012048259A2 (en) | 2010-10-08 | 2011-10-07 | Substituted pyridazine carboxamide compounds |
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| CA2813607A1 CA2813607A1 (en) | 2012-04-12 |
| CA2813607C true CA2813607C (en) | 2021-08-31 |
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| WO2011117286A1 (en) * | 2010-03-23 | 2011-09-29 | Basf Se | Pyridazine compounds for controlling invertebrate pests |
| EP2625176B1 (en) * | 2010-10-08 | 2016-08-17 | Xcovery Holding Company LLC | Substitututed 6-amino-pyridazin-3-yl-carboxamide compounds as protein kinase modulators |
| JP6013029B2 (ja) * | 2012-05-25 | 2016-10-25 | 千葉県 | 抗癌剤 |
| RU2550346C2 (ru) * | 2013-09-26 | 2015-05-10 | Общество с ограниченной ответственностью "Отечественные Фармацевтические Технологии" ООО"ФармТех" | Новые химические соединения (варианты) и их применение для лечения онкологических заболеваний |
| CN105085550B (zh) * | 2014-05-21 | 2017-05-24 | 海门慧聚药业有限公司 | 一类alk激酶抑制剂及其制备方法 |
| RU2015110071A (ru) * | 2015-03-23 | 2016-10-10 | Общество с ограниченной ответственностью "Отечественные Фармацевтические Технологии" ООО "ФармТех" | Применение новых химических соединений (варианты) в качестве ингибиторов nuak1 киназы для лечения онкологических заболеваний |
| TWI646094B (zh) * | 2016-06-01 | 2019-01-01 | 大陸商貝達藥業股份有限公司 | Crystal form of inhibitory protein kinase active compound and application thereof |
| RU2631430C1 (ru) * | 2016-10-26 | 2017-09-22 | Общество С Ограниченной Ответственностью "Отечественные Фармацевтические Технологии" | НОВЫЙ СПОСОБ СИНТЕЗА ПРОИЗВОДНЫХ ТЕТРАГИДРОПИРАЗИНО[2,3-c]ПИРИДАЗИНА |
| EP3778590A4 (en) | 2018-04-09 | 2021-12-22 | ShanghaiTech University | ANTI PROTEIN DEGRADATION COMPOUND, ANTITUMOR APPLICATION, INTERMEDIATE THEREOF, AND INTERMEDIATE USE |
| EP3932922A4 (en) | 2019-02-25 | 2022-05-11 | ShanghaiTech University | SULPHUR-CONTAINING COMPOUND BASED ON A GLUTARIMIDE FRAMEWORK AND ITS USE |
| WO2021023233A1 (zh) | 2019-08-05 | 2021-02-11 | 上海科技大学 | Egfr蛋白降解剂及其抗肿瘤应用 |
| WO2022031636A1 (en) | 2020-08-03 | 2022-02-10 | Teva Pharmaceuticals International Gmbh | Solid state forms of ensartinib and ensartinib salts |
| CN117897156A (zh) * | 2021-08-10 | 2024-04-16 | 贝达药业股份有限公司 | 恩沙替尼或其盐在治疗携带met 14外显子跳跃突变的疾病中的用途 |
| CN116082110B (zh) * | 2023-01-09 | 2024-04-12 | 北京肿瘤医院(北京大学肿瘤医院) | 一种11c标记靶向间变性淋巴瘤激酶alk突变分子探针及应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4369172A (en) | 1981-12-18 | 1983-01-18 | Forest Laboratories Inc. | Prolonged release therapeutic compositions based on hydroxypropylmethylcellulose |
| DE3583799D1 (de) | 1985-01-11 | 1991-09-19 | Abbott Lab Ltd | Feste zubereitung mit langsamer freisetzung. |
| JP2773959B2 (ja) | 1990-07-10 | 1998-07-09 | 信越化学工業株式会社 | 大腸内放出性固形製剤 |
| UA73092C2 (uk) | 1998-07-17 | 2005-06-15 | Брістол-Майерс Сквібб Компані | Таблетка з ентеросолюбільним покриттям і спосіб її приготування |
| EP1101490B1 (en) | 1998-07-28 | 2005-04-13 | Tanabe Seiyaku Co., Ltd. | Preparation capable of releasing drug at target site in intestine |
| US6461631B1 (en) | 1999-11-16 | 2002-10-08 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
| US6800663B2 (en) | 2002-10-18 | 2004-10-05 | Alkermes Controlled Therapeutics Inc. Ii, | Crosslinked hydrogel copolymers |
| PT2476667E (pt) | 2003-02-26 | 2014-09-18 | Sugen Inc | Compostos de aminoheteroarilo como inibidores da proteína quinase |
| EP1786777A1 (en) * | 2004-08-26 | 2007-05-23 | Pfizer, Inc. | Aminoheteroaryl compounds as protein tyrosine kinase inhibitors |
| CA2577937C (en) | 2004-08-26 | 2010-12-21 | Pfizer Inc. | Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors |
| CA2675755C (en) * | 2007-01-19 | 2015-10-06 | Xcovery, Inc. | Pyridine and pyridazine derivatives as kinase inhibitors |
| KR101691640B1 (ko) * | 2008-06-19 | 2016-12-30 | 엑스커버리 홀딩 컴퍼니 엘엘씨 | 키나아제 억제제 화합물로서의 치환된 피리다진 카르복사마이드 화합물 |
| EP2625176B1 (en) * | 2010-10-08 | 2016-08-17 | Xcovery Holding Company LLC | Substitututed 6-amino-pyridazin-3-yl-carboxamide compounds as protein kinase modulators |
| EA025030B1 (ru) * | 2010-10-08 | 2016-11-30 | Икскавери Холдинг Кампани, Ллс | Соединение {5-[(1r)-1-(2,6-дихлор-3-фторфенил)этокси]-6-аминопиридазин-3-ил}-n-(1-метил-6-оксо-1,6-дигидропиридин-3-ил)карбоксамид в качестве киназного ингибитора |
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- 2011-10-07 WO PCT/US2011/055428 patent/WO2012048259A2/en not_active Ceased
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| Publication number | Publication date |
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| JP6235078B2 (ja) | 2017-11-22 |
| EP2625176B1 (en) | 2016-08-17 |
| EP2625176A4 (en) | 2014-04-09 |
| KR101886812B1 (ko) | 2018-08-08 |
| US9126947B2 (en) | 2015-09-08 |
| EA024809B1 (ru) | 2016-10-31 |
| JP2016216475A (ja) | 2016-12-22 |
| EP2625176A2 (en) | 2013-08-14 |
| CN103298806B (zh) | 2015-03-18 |
| WO2012048259A2 (en) | 2012-04-12 |
| JP2013539765A (ja) | 2013-10-28 |
| US20130190298A1 (en) | 2013-07-25 |
| WO2012048259A3 (en) | 2012-06-28 |
| ES2610226T3 (es) | 2017-04-26 |
| BR112013008523B1 (pt) | 2021-12-07 |
| EA201390520A1 (ru) | 2013-09-30 |
| BR112013008523A2 (pt) | 2016-07-12 |
| CN103298806A (zh) | 2013-09-11 |
| CA2813607A1 (en) | 2012-04-12 |
| AU2011311814B2 (en) | 2016-12-22 |
| US20180016240A1 (en) | 2018-01-18 |
| PL2625176T3 (pl) | 2017-08-31 |
| KR20130141514A (ko) | 2013-12-26 |
| US20160068493A1 (en) | 2016-03-10 |
| AU2011311814A1 (en) | 2013-05-02 |
| JP6023062B2 (ja) | 2016-11-09 |
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