(5-Chloropyridin-3-yl) 1,3-benzodioxole-5-carboxylate | 1026494-94-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (5-Chloropyridin-3-yl) 1,3-benzodioxole-5-carboxylate
• CAS: 1026494-94-9
• 化学式: C₁₃H₈ClNO₄
• 分子量: 277.664
• InChiKey: VLKCKSUXXZIUHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氯-3-羟基吡啶 、 胡椒酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (5-Chloropyridin-3-yl) 1,3-benzodioxole-5-carboxylate
  参考文献：
  名称：

  Heteroaromatic ester inhibitors of hepatitis A virus 3C proteinase: Evaluation of mode of action

  摘要：

  The related 3C and 3C-like proteinase (3C(pro) and 3CL(pro)) of picornaviruses and coronaviruses, respectively, are good drug targets. As part of an effort to generate broad-spectrum inhibitors of these enzymes, we screened a library of inhibitors based on a halopyridinyl ester from a previous study of the severe acute respiratory syndrome (SARS) 3CL proteinase against Hepatitis A virus (HAV) 3C(pro). Three of the compounds, which also had furan rings, inhibited the cleavage activity of HAV 3C(pro) with K-icS of 120-240 nM. HPLC-based assays revealed that the inhibitors were slowly hydrolyzed by both HAV 3C(pro) and SARS 3CL(pro), confirming the identity of the expected products. Mass spectrometric analyses indicated that this hydrolysis proceeded via an acylenzyme intermediate. Modeling studies indicated that the halopyridinyl moiety of the inhibitor fits tightly into the S1-binding pocket, consistent with the lack of tolerance of the inhibitors to modi. cation in this portion of the molecule. These compounds are among the most potent non-peptidic inhibitors reported to date against a 3C(pro). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.03.059

文献信息

• Heteroaromatic ester inhibitors of hepatitis A virus 3C proteinase: Evaluation of mode of action
  作者：Carly Huitema、Jianmin Zhang、Jiang Yin、Michael N.G. James、John C. Vederas、Lindsay D. Eltis

  DOI：10.1016/j.bmc.2008.03.059

  日期：2008.5

  The related 3C and 3C-like proteinase (3C(pro) and 3CL(pro)) of picornaviruses and coronaviruses, respectively, are good drug targets. As part of an effort to generate broad-spectrum inhibitors of these enzymes, we screened a library of inhibitors based on a halopyridinyl ester from a previous study of the severe acute respiratory syndrome (SARS) 3CL proteinase against Hepatitis A virus (HAV) 3C(pro). Three of the compounds, which also had furan rings, inhibited the cleavage activity of HAV 3C(pro) with K-icS of 120-240 nM. HPLC-based assays revealed that the inhibitors were slowly hydrolyzed by both HAV 3C(pro) and SARS 3CL(pro), confirming the identity of the expected products. Mass spectrometric analyses indicated that this hydrolysis proceeded via an acylenzyme intermediate. Modeling studies indicated that the halopyridinyl moiety of the inhibitor fits tightly into the S1-binding pocket, consistent with the lack of tolerance of the inhibitors to modi. cation in this portion of the molecule. These compounds are among the most potent non-peptidic inhibitors reported to date against a 3C(pro). (C) 2008 Elsevier Ltd. All rights reserved.