2-({6-[2-(Bis-benzyloxy-phosphoryl)-1-methoxycarbonyl-ethylcarbamoyl]-1H-benzoimidazol-2-yl}-difluoro-methyl)-3-methyl-3H-benzoimidazole-5-carboxylic acid | 596803-03-1

• 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: 2-({6-[2-(Bis-benzyloxy-phosphoryl)-1-methoxycarbonyl-ethylcarbamoyl]-1H-benzoimidazol-2-yl}-difluoro-methyl)-3-methyl-3H-benzoimidazole-5-carboxylic acid
• CAS: 596803-03-1
• 化学式: C₃₆H₃₂F₂N₅O₈P
• 分子量: 731.649
• InChiKey: XSTABROJWSQDFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.19
• 重原子数：
  52.0
• 可旋转键数：
  14.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  174.73
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2-({6-[2-(Bis-benzyloxy-phosphoryl)-1-methoxycarbonyl-ethylcarbamoyl]-1H-benzoimidazol-2-yl}-difluoro-methyl)-3-methyl-3H-benzoimidazole-5-carboxylic acid 在 palladium on activated charcoal 盐酸 、 lithium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-{[2-({6-[1-(1-Carboxy-2-phosphono-ethylcarbamoyl)-2-phosphono-ethylcarbamoyl]-1-methyl-1H-benzoimidazol-2-yl}-difluoro-methyl)-3H-benzoimidazole-5-carbonyl]-amino}-3-phosphono-propionic acid
  参考文献：
  名称：

  Highly potent non-peptidic inhibitors of the HCV NS3/NS4A serine protease

  摘要：

  Screening of a diverse set of bisbenzimidazoles for inhibition of the hepatitis C virus (HCV) serine protease NS3/NS4A led to the identification of a potent Zn2+-dependent inhibitor (1). Optimization of this screening hit afforded a 10-fold more potent inhibitor (46) under Zn2+ conditions (K-i = 27 nM). This compound (46) binds also to NS3/NS4A in a Zn2+ independent fashion (K-i = 1 muM). The SAR of this class of compounds under Zn2+ conditions is highly divergent compared to the SAR in the absence of Zn2+, suggesting two distinct binding modes. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00680-7
• 作为产物：
  描述：

  2-Methoxycarbonylmethyl-3H-benzoimidazole-5-carboxylic acid methyl ester 在 lithium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N-氟代双苯磺酰胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-({6-[2-(Bis-benzyloxy-phosphoryl)-1-methoxycarbonyl-ethylcarbamoyl]-1H-benzoimidazol-2-yl}-difluoro-methyl)-3-methyl-3H-benzoimidazole-5-carboxylic acid
  参考文献：
  名称：

  Highly potent non-peptidic inhibitors of the HCV NS3/NS4A serine protease

  摘要：

  Screening of a diverse set of bisbenzimidazoles for inhibition of the hepatitis C virus (HCV) serine protease NS3/NS4A led to the identification of a potent Zn2+-dependent inhibitor (1). Optimization of this screening hit afforded a 10-fold more potent inhibitor (46) under Zn2+ conditions (K-i = 27 nM). This compound (46) binds also to NS3/NS4A in a Zn2+ independent fashion (K-i = 1 muM). The SAR of this class of compounds under Zn2+ conditions is highly divergent compared to the SAR in the absence of Zn2+, suggesting two distinct binding modes. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00680-7