CN102627620A - 一类苯并呋喃衍生物及其医药应用 - Google Patents
一类苯并呋喃衍生物及其医药应用 Download PDFInfo
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Abstract
Description
化合物 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | Olaparib |
活性强度 | ++ | +++ | ++ | +++ | ++ | ++ | ++ | + | + | +++ |
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Cited By (7)
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WO2013117120A1 (zh) * | 2012-02-09 | 2013-08-15 | 中国科学院上海药物研究所 | 2-芳基苯并呋喃-7-甲酰胺类化合物、其制备方法及用途 |
CN108699019A (zh) * | 2015-11-11 | 2018-10-23 | 华纳巴布科克绿色化学学院有限公司 | 用于治疗中枢神经系统和其他疾病的苯并呋喃衍生物 |
WO2018228205A1 (zh) * | 2017-06-14 | 2018-12-20 | 中国科学院上海药物研究所 | 盐酸美呋哌瑞多晶型物及其制备方法与应用 |
CN109810100A (zh) * | 2017-11-21 | 2019-05-28 | 中国药科大学 | 含有苯并呋喃的parp-1和pi3k双靶点抑制剂 |
WO2020119772A1 (zh) * | 2018-12-14 | 2020-06-18 | 中国科学院上海药物研究所 | 盐酸美呋哌瑞多晶型物及其制备方法 |
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RU2783418C1 (ru) * | 2018-05-31 | 2022-11-14 | Шангхаи Институте Оф Материа Медика, Чайнесе Академи Оф Сайнсес | Способ получения полиморфа гидрохлорида 2-[4-(метиламинометил)фенил]-5-фтор-бензофуран-7-карбоксамида |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000029384A1 (de) * | 1998-11-17 | 2000-05-25 | Basf Aktiengesellschaft | 2-phenylbenzimidazole und 2-phenylindole, deren herstellung und anwendung |
US7087637B2 (en) * | 2000-05-11 | 2006-08-08 | Basf Ag | Substituted indoles which are PARP inhibitors |
CN101641014A (zh) * | 2006-12-28 | 2010-02-03 | 艾博特公司 | 聚(adp-核糖)聚合酶抑制剂 |
CN103242273A (zh) * | 2012-02-09 | 2013-08-14 | 中国科学院上海药物研究所 | 2-芳基苯并呋喃-7-甲酰胺类化合物、其制备方法及用途 |
-
2012
- 2012-04-10 CN CN201210104623.4A patent/CN102627620B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000029384A1 (de) * | 1998-11-17 | 2000-05-25 | Basf Aktiengesellschaft | 2-phenylbenzimidazole und 2-phenylindole, deren herstellung und anwendung |
US7087637B2 (en) * | 2000-05-11 | 2006-08-08 | Basf Ag | Substituted indoles which are PARP inhibitors |
CN101641014A (zh) * | 2006-12-28 | 2010-02-03 | 艾博特公司 | 聚(adp-核糖)聚合酶抑制剂 |
CN103242273A (zh) * | 2012-02-09 | 2013-08-14 | 中国科学院上海药物研究所 | 2-芳基苯并呋喃-7-甲酰胺类化合物、其制备方法及用途 |
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JP2015511942A (ja) * | 2012-02-09 | 2015-04-23 | 上海 インスティテュート オブ マテリア メディカ、チャイニーズ アカデミー オブ サイエンシーズShanghai Institute Of Materia Medica, Chinese Academy Of Sciences | 2−アリールベンゾフラン−7−カルボキサミド系化合物、その製造方法および用途 |
US9533965B2 (en) | 2012-02-09 | 2017-01-03 | Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences | 2-arylbenzofuran-7-formamide compounds, preparation method and use thereof |
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RU2783418C9 (ru) * | 2017-06-14 | 2023-02-20 | Шангхаи Институте Оф Материа Медика, Чайнесе Академи Оф Сайнсес | Способ получения полиморфа гидрохлорида 2-[4-(метиламинометил)фенил]-5-фтор-бензофуран-7-карбоксамида |
US11174237B2 (en) | 2017-06-14 | 2021-11-16 | Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences | 2-[4-(meihylaminomethyl)phenyl]-5-fluoro- benzofuran-7-carboxamide hydrochloride polymorph, preparation method therefor and application thereof |
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RU2783418C1 (ru) * | 2018-05-31 | 2022-11-14 | Шангхаи Институте Оф Материа Медика, Чайнесе Академи Оф Сайнсес | Способ получения полиморфа гидрохлорида 2-[4-(метиламинометил)фенил]-5-фтор-бензофуран-7-карбоксамида |
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