(S,E)-2-[2-[4-(3-(1H-indol-3-yl)-3-oxoprop-1-enyl)-phenoxy]acetamido]-3-phenylpropanoic acid | 1269423-80-4

• 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: (S,E)-2-[2-[4-(3-(1H-indol-3-yl)-3-oxoprop-1-enyl)-phenoxy]acetamido]-3-phenylpropanoic acid
• 英文别名: (2S)-2-[[2-[4-[(E)-3-(1H-indol-3-yl)-3-oxoprop-1-enyl]phenoxy]acetyl]amino]-3-phenylpropanoic acid
• CAS: 1269423-80-4
• 化学式: C₂₈H₂₄N₂O₅
• 分子量: 468.509
• InChiKey: YBEOSVCIUFIFFR-FHWWYNCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S,E)-methyl 2-[2-[4-(3-(1H-indol-3-yl)-3-oxoprop-1-enyl)-phenoxy]acetamido]-3-phenylpropanoate 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 3.0h， 以88%的产率得到(S,E)-2-[2-[4-(3-(1H-indol-3-yl)-3-oxoprop-1-enyl)-phenoxy]acetamido]-3-phenylpropanoic acid
  参考文献：
  名称：

  Molecular modeling based approach, synthesis and in vitro assay to new indole inhibitors of hepatitis C NS3/4A serine protease

  摘要：

  In an attempt to identify potential HCV NS3 protease inhibitors lead compounds, a series of novel indoles (10a-g) was designed. Molecular modeling study, including fitting to a 3D-pharmacophore model of the designed molecules (10a-g), with HCV NS3 protease hypothesis using CATALYST program was fulfilled. Also, the molecular docking into the NS3 active site was examined using Discovery Studio 2.5 software. Several compounds showed significant high simulation docking score and fit values. The designed compounds with high docking score and fit values were synthesized and biologically evaluated in vitro using an NS3 protease binding assay. It appears that most of the tested compounds reveal promising inhibitory activity against NS3 protease. Of these, compounds 10a and 10b demonstrated potent HCV NS3 protease inhibitors with IC50 values of 9 and 12 mu g/mL, respectively. The experimental serine protease inhibitor activities of compounds 10a-g were consistent with their molecular modeling results. Inhibitors from this class have promising characteristics for further development as anti-HCV agents. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.017

文献信息

• Molecular modeling based approach, synthesis and in vitro assay to new indole inhibitors of hepatitis C NS3/4A serine protease
  作者：Nasser S.M. Ismail、Masao Hattori

  DOI：10.1016/j.bmc.2010.11.017

  日期：2011.1

  In an attempt to identify potential HCV NS3 protease inhibitors lead compounds, a series of novel indoles (10a-g) was designed. Molecular modeling study, including fitting to a 3D-pharmacophore model of the designed molecules (10a-g), with HCV NS3 protease hypothesis using CATALYST program was fulfilled. Also, the molecular docking into the NS3 active site was examined using Discovery Studio 2.5 software. Several compounds showed significant high simulation docking score and fit values. The designed compounds with high docking score and fit values were synthesized and biologically evaluated in vitro using an NS3 protease binding assay. It appears that most of the tested compounds reveal promising inhibitory activity against NS3 protease. Of these, compounds 10a and 10b demonstrated potent HCV NS3 protease inhibitors with IC50 values of 9 and 12 mu g/mL, respectively. The experimental serine protease inhibitor activities of compounds 10a-g were consistent with their molecular modeling results. Inhibitors from this class have promising characteristics for further development as anti-HCV agents. (C) 2010 Elsevier Ltd. All rights reserved.