6-(5-methoxy-1H-indol-3-yl)-6-(4-(trifluoromethyl)phenyl)-4-oxohexanoic acid | 1072881-34-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 6-(5-methoxy-1H-indol-3-yl)-6-(4-(trifluoromethyl)phenyl)-4-oxohexanoic acid
• CAS: 1072881-34-5
• 化学式: C₂₂H₂₀F₃NO₄
• 分子量: 419.4
• InChiKey: LQNLKSKBVKBAJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.15
• 重原子数：
  30.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.39
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  6-(5-methoxy-1H-indol-3-yl)-6-(4-(trifluoromethyl)phenyl)-4-oxohexanoic acid 、 L-苯丙氨酸甲酯 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89%的产率得到methyl (2S)-2-[6-(5-methoxy-1H-indol-3-yl)-6-(4-(trifluoromethyl)phenyl)-4-oxohexanamido]-3-phenyl-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
• 作为产物：
  描述：

  5-甲氧基吲哚 、 (E)-6-[4-(trifluoromethyl)phenyl]-4-oxohex-5-enoic acid 在 碘 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以88%的产率得到6-(5-methoxy-1H-indol-3-yl)-6-(4-(trifluoromethyl)phenyl)-4-oxohexanoic 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