5-(thiophen-2-yl)-(1,3)dioxolo(4,5-d)pyriMidine-7-carboxylic acid | 766557-57-7

• 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-(thiophen-2-yl)-(1,3)dioxolo(4,5-d)pyriMidine-7-carboxylic acid
• 英文别名: 5-thiophen-2-yl-[1,3]dioxolo[4,5-d]pyrimidine-7-carboxylic acid
• CAS: 766557-57-7
• 化学式: C₁₀H₆N₂O₄S
• 分子量: 250.235
• InChiKey: MGFDVLDLQNZUBH-UHFFFAOYSA-N

物化性质

• 沸点：
  352.4±42.0 °C(Predicted)
• 密度：
  1.621±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(thiophen-2-yl)-(1,3)dioxolo(4,5-d)pyriMidine-7-carboxylic acid 在 4-二甲氨基吡啶 、 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 N-(5,6-Dihydroxy-2-thiophen-2-yl-pyrimidine-4-carbonyl)-C,C,C-trifluoro-methanesulfonamide
  参考文献：
  名称：

  Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid

  摘要：

  5,6-Dihydroxypyrimidine-4-carboxylic acids are a promising series of hepatitis C virus (HCV) NS5B polymerase inhibitors that bind at the active site of the enzyme. Here we report a simple 2-thienyl substituted analogue that shows 10-fold improved activity over the original lead, and which allowed us to further delineate the key elements of the pharmacophore of this class of inhibitor. This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.075
• 作为产物：
  描述：

  methyl 5-thiophen-2-yl-[1,3]dioxolo[4,5-d]pyrimidine-7-carboxylate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.03h， 以75%的产率得到5-(thiophen-2-yl)-(1,3)dioxolo(4,5-d)pyriMidine-7-carboxylic acid
  参考文献：
  名称：

  Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid

  摘要：

  5,6-Dihydroxypyrimidine-4-carboxylic acids are a promising series of hepatitis C virus (HCV) NS5B polymerase inhibitors that bind at the active site of the enzyme. Here we report a simple 2-thienyl substituted analogue that shows 10-fold improved activity over the original lead, and which allowed us to further delineate the key elements of the pharmacophore of this class of inhibitor. This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.075