CN105348169A - 一种组蛋白去乙酰酶抑制剂(e)-3-(2-(1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1氢-吲哚-3-基)乙酰氨基)-n-羟基丁-2-烯酰胺及其制备方法和应用 - Google Patents
一种组蛋白去乙酰酶抑制剂(e)-3-(2-(1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1氢-吲哚-3-基)乙酰氨基)-n-羟基丁-2-烯酰胺及其制备方法和应用 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
Abstract
Description
Claims (6)
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CN201510782517.5A CN105348169B (zh) | 2015-11-16 | 2015-11-16 | 一种组蛋白去乙酰酶抑制剂(e)‑3‑(2‑(1‑(4‑氯苯甲酰基)‑5‑甲氧基‑2‑甲基‑1氢‑吲哚‑3‑基)乙酰氨基)‑n‑羟基丁‑2‑烯酰胺及其制备方法和应用 |
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CN107141244A (zh) * | 2017-05-08 | 2017-09-08 | 潍坊博创国际生物医药研究院 | 吲哚丁酸类组蛋白去乙酰酶抑制剂及其制备方法和应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006099416A1 (en) * | 2005-03-11 | 2006-09-21 | Nitromed, Inc. | 2-methyl indole cyclooxygenase-2 selective inhibitors, compositions and methods of use |
CN102659630A (zh) * | 2011-05-04 | 2012-09-12 | 成都地奥九泓制药厂 | 一种异羟肟酸类化合物及其制备方法和用途 |
CN102947268A (zh) * | 2010-03-29 | 2013-02-27 | 台北医学大学 | 吲哚基或吲哚啉基羟肟酸化合物 |
CN103906732A (zh) * | 2011-10-28 | 2014-07-02 | 株式会社钟根堂 | 用作hdac抑制剂的异羟肟酸酯衍生物以及包含所述衍生物的药物组合物 |
CN104324025A (zh) * | 2005-08-03 | 2015-02-04 | 诺华股份有限公司 | Hdac抑制剂在治疗骨髓瘤中的用途 |
-
2015
- 2015-11-16 CN CN201510782517.5A patent/CN105348169B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006099416A1 (en) * | 2005-03-11 | 2006-09-21 | Nitromed, Inc. | 2-methyl indole cyclooxygenase-2 selective inhibitors, compositions and methods of use |
CN104324025A (zh) * | 2005-08-03 | 2015-02-04 | 诺华股份有限公司 | Hdac抑制剂在治疗骨髓瘤中的用途 |
CN102947268A (zh) * | 2010-03-29 | 2013-02-27 | 台北医学大学 | 吲哚基或吲哚啉基羟肟酸化合物 |
CN102659630A (zh) * | 2011-05-04 | 2012-09-12 | 成都地奥九泓制药厂 | 一种异羟肟酸类化合物及其制备方法和用途 |
CN103906732A (zh) * | 2011-10-28 | 2014-07-02 | 株式会社钟根堂 | 用作hdac抑制剂的异羟肟酸酯衍生物以及包含所述衍生物的药物组合物 |
Non-Patent Citations (2)
Title |
---|
周玉美,等: "组蛋白去乙酰酶抑制剂的构效关系研究进展", 《解放军药学学报》 * |
王欣,等: "组蛋白去乙酰酶抑制剂的研究进展", 《中国药物化学杂志》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107141244A (zh) * | 2017-05-08 | 2017-09-08 | 潍坊博创国际生物医药研究院 | 吲哚丁酸类组蛋白去乙酰酶抑制剂及其制备方法和应用 |
CN107141244B (zh) * | 2017-05-08 | 2019-11-19 | 潍坊医学院 | 吲哚丁酸类组蛋白去乙酰酶抑制剂及其制备方法和应用 |
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