(2S)-3-[5-(carboxymethyloxy)-1H-indol-3-yl]-2-[[1-cyclohexyl-2-(3-furyl)benzimidazole-5-carbonyl]amino]propanoic acid

• 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: (2S)-3-[5-(carboxymethyloxy)-1H-indol-3-yl]-2-[[1-cyclohexyl-2-(3-furyl)benzimidazole-5-carbonyl]amino]propanoic acid
• 英文别名: (2S)-3-[5-(carboxymethoxy)-1H-indol-3-yl]-2-[[1-cyclohexyl-2-(furan-3-yl)benzimidazole-5-carbonyl]amino]propanoic acid
• 化学式: C₃₁H₃₀N₄O₇
• 分子量: 570.602
• InChiKey: ISZHARSXKHHLKL-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-羟基-L-色氨酸 在 盐酸 、 氯化亚砜 、 caesium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 丙酮 为溶剂， 生成 (2S)-3-[5-(carboxymethyloxy)-1H-indol-3-yl]-2-[[1-cyclohexyl-2-(3-furyl)benzimidazole-5-carbonyl]amino]propanoic acid
  参考文献：
  名称：

  Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase: discovery of benzimidazole 5-carboxylic amide derivatives with low-nanomolar potency

  摘要：

  Optimization of benzimidazole 5-carboxamide derivatives previously identified as specific inhibitors of the NS5B polymerase of the hepatitis C virus (HCV) has led to the discovery of potent analogues that inhibit the enzyme at low-nanomolar concentrations. Greater than 800-fold improvement in potency from the original lead structure was achieved through the combined effects of conformational rigidification, molecular size extension and the identification of previously unexploited interactions. Furthermore, these inhibitors retain specificity for HCV polymerase relative to other viral and mammalian RNA polymerases. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.032

文献信息

• NON-NUCLEOSIDE ANTI-HEPACIVIRUS AGENTS AND USES THEREOF
  申请人：Boyd A. Vincent

  公开号：US20070021434A1

  公开（公告）日：2007-01-25

  The present dislcosure provides amide-based, non-nucleoside compounds having antiviral activity against Hepacivirus, such as hepatitis C virus (HCV), methods and intermediates for synthesizing such compounds, and methods of using the compounds in a variety of contexts, including in the treatment and prevention of viral infections. The present dislcosure also provides methods for identifying amide-based, non-nucleoside compounds having antiviral activity.

  本公开提供了基于酰胺的非核苷类化合物，具有抗Hepacivirus活性，例如丙型肝炎病毒（HCV），合成这类化合物的方法和中间体，以及在各种情境中使用这些化合物的方法，包括在治疗和预防病毒感染中的应用。本公开还提供了识别具有抗病毒活性的基于酰胺的非核苷类化合物的方法。
• Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase: discovery of benzimidazole 5-carboxylic amide derivatives with low-nanomolar potency
  作者：Pierre L Beaulieu、Michael Bös、Yves Bousquet、Patrick DeRoy、Gulrez Fazal、Jean Gauthier、James Gillard、Sylvie Goulet、Ginette McKercher、Marc-André Poupart、Serge Valois、George Kukolj

  DOI：10.1016/j.bmcl.2003.12.032

  日期：2004.2

  Optimization of benzimidazole 5-carboxamide derivatives previously identified as specific inhibitors of the NS5B polymerase of the hepatitis C virus (HCV) has led to the discovery of potent analogues that inhibit the enzyme at low-nanomolar concentrations. Greater than 800-fold improvement in potency from the original lead structure was achieved through the combined effects of conformational rigidification, molecular size extension and the identification of previously unexploited interactions. Furthermore, these inhibitors retain specificity for HCV polymerase relative to other viral and mammalian RNA polymerases. (C) 2003 Elsevier Ltd. All rights reserved.