1-[3-(2-hydroxycarbamoylvinyl)benzenesulfonyl]-1H-indole-3-carboxylic acid dimethylamide

• 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: 1-[3-(2-hydroxycarbamoylvinyl)benzenesulfonyl]-1H-indole-3-carboxylic acid dimethylamide
• 化学式: C₂₀H₁₉N₃O₅S
• 分子量: 413.454
• InChiKey: FHSWKNWDBKVHSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  108.71
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  3-溴苯磺酰氯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hydride 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 1-[3-(2-hydroxycarbamoylvinyl)benzenesulfonyl]-1H-indole-3-carboxylic acid dimethylamide
  参考文献：
  名称：

  Ring-opened tetrahydro-γ-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms

  摘要：

  This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5-18) were synthesized and structure -activity relationship studies indicated that the change of the tetrahydro-gamma-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials. In addition, attachment of different hydroxamic acid groups, the zinc binding motif at the N1 position, contributes to the antiproliferative activity in cancer cells. Several synthetic compounds exhibited potent growth inhibition in a broad spectrum of tumor cell lines, induced irreversible growth arrest capacities by suppressing colony formation ability and activated the apoptosis pathway. The data provide compelling evidence that our newly synthesized compounds with type B to D hydroxamic acid groups as the zinc binding motif at the N1 position are potent selective inhibitors of HDAC6 and could be investigated preclinically as potential anticancer drugs. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.12.039

文献信息

• Ring-opened tetrahydro-γ-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms
  作者：Kunal Nepali、Hsueh-Yun Lee、Mei-Jung Lai、Ritu Ojha、Tung-Yun Wu、Gu-Xian Wu、Mei-Chuan Chen、Jing-Ping Liou

  DOI：10.1016/j.ejmech.2016.12.039

  日期：2017.2

  This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5-18) were synthesized and structure -activity relationship studies indicated that the change of the tetrahydro-gamma-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials. In addition, attachment of different hydroxamic acid groups, the zinc binding motif at the N1 position, contributes to the antiproliferative activity in cancer cells. Several synthetic compounds exhibited potent growth inhibition in a broad spectrum of tumor cell lines, induced irreversible growth arrest capacities by suppressing colony formation ability and activated the apoptosis pathway. The data provide compelling evidence that our newly synthesized compounds with type B to D hydroxamic acid groups as the zinc binding motif at the N1 position are potent selective inhibitors of HDAC6 and could be investigated preclinically as potential anticancer drugs. (C) 2016 Elsevier Masson SAS. All rights reserved.