(E)-N-hydroxy-3-{4-[3-(2-methyl-1H-indol-3-yl)pyrrolidin-1-ylmethyl]phenyl}acrylamide | 1218928-86-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮
• 英文名称: (E)-N-hydroxy-3-{4-[3-(2-methyl-1H-indol-3-yl)pyrrolidin-1-ylmethyl]phenyl}acrylamide
• 英文别名: (E)-N-hydroxy-3-[4-[[3-(2-methyl-1H-indol-3-yl)pyrrolidin-1-yl]methyl]phenyl]prop-2-enamide
• CAS: 1218928-86-9
• 化学式: C₂₃H₂₅N₃O₂
• 分子量: 375.47
• InChiKey: UJYVIAFJOKZQLT-ZHACJKMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  68.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-N-hydroxy-3-{4-[3-(2-methyl-1H-indol-3-yl)pyrrolidin-1-ylmethyl]phenyl}acrylamide 在 Chiralpak AD-H 作用下， 以 hexanes 、 异丙醇 为溶剂， 生成 (E)-N-hydroxy-3-{4-[(R)-3-(2-methyl-1H-indol-3-yl)pyrrolidin-1-ylmethyl]phenyl}acrylamide 、 (E)-N-hydroxy-3-{4-[(S)-3-(2-methyl-1H-indol-3-yl)pyrrolidin-1-ylmethyl]phenyl}acrylamide
  参考文献：
  名称：

  [EN] HYDROXAMATE-BASED INHIBITORS OF DEACETYLASES
  [FR] COMPOSÉS À BASE D'HYDROXAMATE EN TANT QU'INHIBITEURS DES DÉSACÉTYLASES

  摘要：

  本教导涉及公式（I）的化合物及其药用盐、水合物、酯和前药，其中R1、R2、R3、R4、R5、环A和Z如本文所定义。本教导还提供制备公式（I）化合物的方法，以及利用公式（I）化合物治疗完全或部分由脱乙酰酶介导的病理状况或疾病的方法。

  公开号：

  WO2012025164A1
• 作为产物：
  描述：

  (E)-3-{4-[2-(2-methyl-1H-indol-3-yl)pyrrolidin-1-ylmethyl]phenyl}acrylic acid methyl ester 在 羟胺 、 sodium methylate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.5h， 以87%的产率得到(E)-N-hydroxy-3-{4-[3-(2-methyl-1H-indol-3-yl)pyrrolidin-1-ylmethyl]phenyl}acrylamide
  参考文献：
  名称：

  Conformational Refinement of Hydroxamate-Based Histone Deacetylase Inhibitors and Exploration of 3-Piperidin-3-ylindole Analogues of Dacinostat (LAQ824)

  摘要：

  Inspired by natural product HDAC inhibitors, we prepared a series of conformationally restrained HDAC inhibitors based on the hydroxamic acid dacinostat (LAQ824, 7). Several scaffolds with improved biochemical and cellular potency, as well as attenuated hERG inhibition, were identified, suggesting that the introduction of molecular rigidity is a viable strategy to enhance HDAC binding and mitigate hERG liability. Further SAR studies around a 3-piperidin-3-ylindole moiety resulted in the discovery of compound 30, for which a unique conformation was speculated to contribute to overcoming increased lipophilicity and attenuating h ERG binding. Separation of racemate 30 afforded 32, the R enantiomer, which demonstrated improved potency in both enzyme and cellular assays compared to dacinostat.

  DOI：

  10.1021/jm100007m

文献信息

• Hydroxamate-Based Inhibitors of Deacetylases
  申请人：BROOKS Clinton A.

  公开号：US20110060009A1

  公开（公告）日：2011-03-10

  The present teachings relate to compounds of Formula I: and pharmaceutically acceptable salts, hydrates, esters, and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , ring A, and Z are as defined herein. The present teachings also provide methods of preparing compounds of Formula I and methods of use compounds of Formula I in treating pathologic conditions or disorders mediated wholly or in part by deacetylases.

  本教导涉及Formula I的化合物：及其药用盐、水合物、酯和前药，其中R1、R2、R3、R4、R5、环A和Z的定义如本文所述。本教导还提供制备Formula I化合物的方法，以及利用Formula I化合物治疗完全或部分由去乙酰酶介导的病理状况或疾病的方法。
• HYDROXAMATE-BASED INHIBITORS OF DEACETYLASES
  申请人：Brooks Clinton Alan

  公开号：US20130231373A1

  公开（公告）日：2013-09-05

  The present teachings relate to compounds of Formula (I): and pharmaceutically acceptable salts, hydrates, esters, and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , ring A, and Z are as defined herein. The present teachings also provide methods of preparing compounds of Formula (I) and methods of use compounds of Formula (I) in treating pathologic conditions or disorders mediated wholly or in part by deacetylases.

  本发明涉及公式（I）化合物及其药学上可接受的盐、水合物、酯和前药，其中R1、R2、R3、R4、R5、环A和Z的定义如本文所述。本发明还提供制备公式（I）化合物的方法，以及使用公式（I）化合物治疗完全或部分通过去乙酰化酶介导的病理条件或疾病的方法。