(E)-3-{4-[3-(2-phenyl-1H-indol-3-yl)piperidin-1-ylmethyl]phenyl}acrylic acid methyl ester | 1218928-99-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-3-{4-[3-(2-phenyl-1H-indol-3-yl)piperidin-1-ylmethyl]phenyl}acrylic acid methyl ester
• 英文别名: methyl (E)-3-[4-[[3-(2-phenyl-1H-indol-3-yl)piperidin-1-yl]methyl]phenyl]prop-2-enoate
• CAS: 1218928-99-4
• 化学式: C₃₀H₃₀N₂O₂
• 分子量: 450.58
• InChiKey: SCGDDKZTIBUHBA-ISLYRVAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-{4-[3-(2-phenyl-1H-indol-3-yl)piperidin-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78%的产率得到(E)-N-hydroxy-3-{4-[3-(2-phenyl-1H-indol-3-yl)piperidin-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
• 作为产物：
  描述：

  3-[1-(4-bromobenzyl)piperidin-3-yl]-2-phenyl-1H-indole 、 丙烯酸甲酯（MA） 在 tris-(dibenzylideneacetone)dipalladium(0) 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以62%的产率得到(E)-3-{4-[3-(2-phenyl-1H-indol-3-yl)piperidin-1-ylmethyl]phenyl}acrylic acid methyl ester
  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