(E)-2-[(1-Benzyl-1H-imidazole-2-carboximidoyl)-aminooxy]-but-2-enedioic acid dimethyl ester | 878650-07-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (E)-2-[(1-Benzyl-1H-imidazole-2-carboximidoyl)-aminooxy]-but-2-enedioic acid dimethyl ester
• 英文别名: dimethyl 2-[[amino-(1-benzylimidazol-2-yl)methylidene]amino]oxybut-2-enedioate
• CAS: 878650-07-8
• 化学式: C₁₇H₁₈N₄O₅
• 分子量: 358.354
• InChiKey: WZUVIMRLZZOUSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-2-[(1-Benzyl-1H-imidazole-2-carboximidoyl)-aminooxy]-but-2-enedioic acid dimethyl ester 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 甲酸铵 作用下， 以 甲醇 、 xylene 为溶剂， 反应 2.5h， 生成 5,6-Dihydroxy-2-(1H-imidazol-2-yl)-pyrimidine-4-carboxylic acid methyl ester
  参考文献：
  名称：

  2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase:  Discovery, SAR, Modeling, and Mutagenesis

  摘要：

  Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 mu M), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.

  DOI：

  10.1021/jm051064t
• 作为产物：
  描述：

  1-benzyl-1H-imidazole-2-carbonitrile 在 盐酸羟胺 、 sodium carbonate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 27.0h， 生成 (E)-2-[(1-Benzyl-1H-imidazole-2-carboximidoyl)-aminooxy]-but-2-enedioic acid dimethyl ester
  参考文献：
  名称：

  2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase:  Discovery, SAR, Modeling, and Mutagenesis

  摘要：

  Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 mu M), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.

  DOI：

  10.1021/jm051064t