5,6-Dihydroxy-2-[4-(thiophene-2-carbonylamino)-2-thienyl]pyrimidine-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5,6-Dihydroxy-2-[4-(thiophene-2-carbonylamino)-2-thienyl]pyrimidine-4-carboxylic acid
• 英文别名: 5-hydroxy-6-oxo-2-[4-(thiophene-2-carbonylamino)thiophen-2-yl]-1H-pyrimidine-4-carboxylic acid
• 化学式: C₁₄H₉N₃O₅S₂
• 分子量: 363.375
• InChiKey: ZWHACVORUKFBLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  185
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-硝基噻吩-4-腈 在 palladium on activated charcoal sodium hydroxide 、 盐酸羟胺 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 xylene 为溶剂， 20.0~140.0 ℃ 、101.33 kPa 条件下， 反应 18.0h， 生成 5,6-Dihydroxy-2-[4-(thiophene-2-carbonylamino)-2-thienyl]pyrimidine-4-carboxylic acid
  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