EA023697B1 - ПРИМЕНЕНИЕ КОМБИНАЦИИ ИЗ 7-(2,5-ДИГИДРО-4-ИМИДАЗО[1,2-а]ПИРИДИН-3-ИЛ-2,5-ДИОКСО-1Н-ПИРРОЛ-3-ИЛ)-9-ФТОР-1,2,3,4-ТЕТРАГИДРО-2-(1-ПИПЕРИДИНИЛКАРБОНИЛ)ПИРРОЛО[3,2,1-jk][1,4]БЕНЗОДИАЗЕПИНА И ХИМИОТЕРАПЕВТИЧЕСКОГО АГЕНТА ДЛЯ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННОГО СРЕДСТВА ДЛЯ ЛЕЧЕНИЯ РАКА ЖЕЛУДКА - Google Patents
ПРИМЕНЕНИЕ КОМБИНАЦИИ ИЗ 7-(2,5-ДИГИДРО-4-ИМИДАЗО[1,2-а]ПИРИДИН-3-ИЛ-2,5-ДИОКСО-1Н-ПИРРОЛ-3-ИЛ)-9-ФТОР-1,2,3,4-ТЕТРАГИДРО-2-(1-ПИПЕРИДИНИЛКАРБОНИЛ)ПИРРОЛО[3,2,1-jk][1,4]БЕНЗОДИАЗЕПИНА И ХИМИОТЕРАПЕВТИЧЕСКОГО АГЕНТА ДЛЯ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННОГО СРЕДСТВА ДЛЯ ЛЕЧЕНИЯ РАКА ЖЕЛУДКА Download PDFInfo
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- EA023697B1 EA023697B1 EA201201155A EA201201155A EA023697B1 EA 023697 B1 EA023697 B1 EA 023697B1 EA 201201155 A EA201201155 A EA 201201155A EA 201201155 A EA201201155 A EA 201201155A EA 023697 B1 EA023697 B1 EA 023697B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- fluoro
- imidazo
- dihydro
- mmol
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Landscapes
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| EA201070085A EA018447B1 (ru) | 2007-07-02 | 2008-06-20 | Применение комбинации 7-(2,5-дигидро-4-имидазо[1,2-а]пиридин-3-ил-2,5-диоксо-1н-пиррол-3-ил)-9-фтор-1,2,3,4-тетрагидро-2-(1-пиперидинилкарбонил)пирроло[3,2,1-jk][1,4]бензодиазепина с химиотерапевтическим агентом для лечения злокачественных опухолей |
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| JP5699129B2 (ja) * | 2009-04-14 | 2015-04-08 | イーライ リリー アンド カンパニー | 造血器新生物および白血病の治療のためのベンゾジアゼピン誘導体 |
| WO2013044219A1 (en) * | 2011-09-22 | 2013-03-28 | Bind Biosciences | Methods of treating cancers with therapeutic nanoparticles |
| WO2014050779A1 (ja) * | 2012-09-25 | 2014-04-03 | 第一三共株式会社 | Ｇｓｋ３阻害剤と抗ｄｒ５抗体の組み合わせ |
| US20180110780A1 (en) * | 2015-04-30 | 2018-04-26 | Taiho Pharmaceutical Co., Ltd. | Agent for alleviating side effect of antitumor drug |
| US10201540B2 (en) | 2016-03-02 | 2019-02-12 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I |
| US10016507B2 (en) * | 2016-03-02 | 2018-07-10 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: III |
| US10213511B2 (en) * | 2016-03-02 | 2019-02-26 | Frequency Therapeutics, Inc. | Thermoreversible compositions for administration of therapeutic agents |
| AU2017386417B2 (en) * | 2016-12-30 | 2022-07-14 | Frequency Therapeutics, Inc. | 1H-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells |
| WO2020163812A1 (en) | 2019-02-08 | 2020-08-13 | Frequency Therapeutics, Inc. | Valproic acid compounds and wnt agonists for treating ear disorders |
| CA3222225A1 (en) * | 2021-06-03 | 2022-12-08 | University Of Cincinnati | Bzd-1 as a chemosensitizer of cancer |
| CN113956157B (zh) * | 2021-11-18 | 2024-05-03 | 西安都创医药科技有限公司 | 一种合成2-甲酰基-1-环丙烷甲酸乙酯的方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1788086A1 (en) * | 1997-03-17 | 2007-05-23 | Human Genome Sciences, Inc. | Death Domain Containing Receptor 5 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8904161D0 (en) * | 1989-02-23 | 1989-04-05 | Hoffmann La Roche | Substituted pyrroles |
| US5376645A (en) * | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
| KR0166088B1 (ko) * | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US7034013B2 (en) * | 2001-03-20 | 2006-04-25 | Cydex, Inc. | Formulations containing propofol and a sulfoalkyl ether cyclodextrin |
| ES2276048T3 (es) * | 2002-03-05 | 2007-06-16 | Eli Lilly And Company | Derivados de purina como inhibidores de cinasa. |
| WO2004026867A2 (en) * | 2002-09-19 | 2004-04-01 | Schering Corporation | Imidazopyridines as cyclin dependent kinase inhibitors |
| CA2569091A1 (en) | 2004-07-09 | 2006-01-19 | Agency For Science, Technology And Research | Modulation of gsk-3.beta. and method of treating proliferative disorders |
| GB0418328D0 (en) * | 2004-08-17 | 2004-09-22 | Imp College Innovations Ltd | Cancer methods and medicaments |
| JP2008541701A (ja) * | 2005-05-04 | 2008-11-27 | ユニヴァーシティ オブ サウス フロリダ | がんの対象における処置応答の予測 |
| TWI428132B (zh) * | 2007-07-02 | 2014-03-01 | Lilly Co Eli | 癌症化療效果之強化 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1788086A1 (en) * | 1997-03-17 | 2007-05-23 | Human Genome Sciences, Inc. | Death Domain Containing Receptor 5 |
Non-Patent Citations (6)
| Title |
|---|
| ENGLER T.A. et al. Substituted 3-imidazo[1,2-a]pyridin-3-yl-4-(1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3. J. Med. Chem., 2004, 47(16), p. 3934-3937, особенно с. 3935, схема 1a, табл. 1, соединение 8, с. 3936, кол. 1 - кол. 2, строка 2 * |
| Handbook of Pharmaceutical Excipients. 5-th Edition, 2006, Pharmaceutical Press, p. 754-756, 770-771, особенно разделы 2, 6, 11 * |
| JAIN A.C. et al. Hygroscopicity, phase solubility and dissolution of various substituted sulfobutylether beta-cyclodextrins (SBE) and danazol-SBE inclusion complexes. Int. J. Pharm., 2001, 212(2), p. 177-86 (реферат) [он-лайн] [Найдено 2011-12-07], Найдено из БД PubMed, PMID: 11165075 * |
| JARHO P. et al. Modified beta-cyclodextrin (SBE7-beta-CyD) with viscous vehicle improves the ocular delivery and tolerability of pilocarpine prodrug in rabbits. J. Pharm. Pharmacol., 1996, 48(3), p. 263-269 (реферат) [он-лайн] [Найдено 2011-12-07], Найдено из БД PubMed, PMID: 8737051 * |
| ROTTMANN S. et al. A TRAIL receptor-dependent synthetic lethal relationship between MYC activation and GSK3beta/FBW7 loss of function. Proceedings of the National Academy of Sciences of the United States of America, 2005,102(42), с. 15195-15200, особенно с. 15197, кол. 1, строки 34-35, c. 15198, кол. 1, строка 24 - кол. 2, строка 13, с. 15199, кол. 2, строки 27-40 * |
| Противоопухолевая химиотерапия. Изд. второе. Под ред. Переводчиковой Н.И., 1993, М., "Медицина", с. 59-61, глава "Рак желудка" * |
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