methyl (2S)-2-[6-(5-bromo-1H-indol-3-yl)-6-(4-methoxyphenyl)-4-oxohexanamido]-3-(1H-indol-3-yl)propanoate | 1072881-44-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S)-2-[6-(5-bromo-1H-indol-3-yl)-6-(4-methoxyphenyl)-4-oxohexanamido]-3-(1H-indol-3-yl)propanoate
• CAS: 1072881-44-7
• 化学式: C₃₃H₃₂BrN₃O₅
• 分子量: 630.538
• InChiKey: WYPLQCDYSDTABP-VXPBITRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.19
• 重原子数：
  42.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  113.28
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[6-(5-bromo-1H-indol-3-yl)-6-(4-methoxyphenyl)-4-oxohexanamido]-3-(1H-indol-3-yl)propanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 以86%的产率得到(2S)-2-[[6-(5-bromo-1H-indol-3-yl)-6-(4-methoxyphenyl)-4-oxo-hexanoyl]amino]-3-(1H-indol-3-yl)propanoic acid
  参考文献：
  名称：

  Computer based design, synthesis and biological evaluation of novel indole derivatives as HCV NS3-4A serine protease inhibitors

  摘要：

  A series of novel indoles were designed and their molecular modeling simulation study including fitting to a 3D pharmacophore model using CATALYST program and their docking into the NS3 active site was examined as HCV NS3 protease inhibitor. Several compounds showed significant high simulation docking score and fit values. The designed compounds were synthesized and biologically evaluated in vitro using an NS3 protease binding assay, where compounds 10a-k showed significant inhibitory activity (>= 67% inhibition at 100 mu g/mL). Of these, compounds 10c and 10f demonstrated potent HCV NS3 protease inhibitors with IC50 values of 15 and 13 mu M, respectively. Enantio-selective Michael addition of an indole derivative in the presence of catalytic amount of AlCl3 and quinine at room temperature afforded the adduct 7e in excellent yield with 73% ee. The product was converted into 101, which showed lower activity than the mixture of the corresponding diastereoisomers. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.084
• 作为产物：
  描述：

  6-(5-bromo-1H-indol-3-yl)-6-(4-methoxyphenyl)-4-oxohexanoic acid 、 L-色氨酸甲酯 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以86%的产率得到methyl (2S)-2-[6-(5-bromo-1H-indol-3-yl)-6-(4-methoxyphenyl)-4-oxohexanamido]-3-(1H-indol-3-yl)propanoate
  参考文献：
  名称：

  Computer based design, synthesis and biological evaluation of novel indole derivatives as HCV NS3-4A serine protease inhibitors

  摘要：

  A series of novel indoles were designed and their molecular modeling simulation study including fitting to a 3D pharmacophore model using CATALYST program and their docking into the NS3 active site was examined as HCV NS3 protease inhibitor. Several compounds showed significant high simulation docking score and fit values. The designed compounds were synthesized and biologically evaluated in vitro using an NS3 protease binding assay, where compounds 10a-k showed significant inhibitory activity (>= 67% inhibition at 100 mu g/mL). Of these, compounds 10c and 10f demonstrated potent HCV NS3 protease inhibitors with IC50 values of 15 and 13 mu M, respectively. Enantio-selective Michael addition of an indole derivative in the presence of catalytic amount of AlCl3 and quinine at room temperature afforded the adduct 7e in excellent yield with 73% ee. The product was converted into 101, which showed lower activity than the mixture of the corresponding diastereoisomers. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.084