(2S)-2-[[6-(5-bromo-1H-indol-3-yl)-4-oxo-6-[4-(trifluoromethyl)phenyl]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid | 1072881-29-8

• 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: (2S)-2-[[6-(5-bromo-1H-indol-3-yl)-4-oxo-6-[4-(trifluoromethyl)phenyl]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid
• CAS: 1072881-29-8
• 化学式: C₃₀H₂₆BrF₃N₂O₅
• 分子量: 631.446
• InChiKey: ITCXJXPXCOIRGX-JVHFYALYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  ethyl (2S)-2-[6-(5-bromo-1H-indol-3-yl)-6-(4-(trifluoromethyl)phenyl)-4-oxohexanamido]-3-(4-hydroxyphenyl)propanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 以83%的产率得到(2S)-2-[[6-(5-bromo-1H-indol-3-yl)-4-oxo-6-[4-(trifluoromethyl)phenyl]hexanoyl]amino]-3-(4-hydroxyphenyl)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

文献信息

• Computer based design, synthesis and biological evaluation of novel indole derivatives as HCV NS3-4A serine protease inhibitors
  作者：Nasser S.M. Ismail、Riham Salah El Dine、Masao Hattori、Kazunori Takahashi、Masataka Ihara

  DOI：10.1016/j.bmc.2008.07.084

  日期：2008.9

  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.