ethyl 3-methoxy-3-((3-methoxy-2-methylphenyl)imino)propanoate | 1428771-40-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl 3-methoxy-3-((3-methoxy-2-methylphenyl)imino)propanoate
• CAS: 1428771-40-7
• 化学式: C₁₄H₁₉NO₄
• 分子量: 265.309
• InChiKey: XGEPOYPKIWHKHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.63
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  57.12
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-methoxy-3-((3-methoxy-2-methylphenyl)imino)propanoate 在 caesium carbonate 、 三乙胺 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 二苯醚 、 二氯甲烷 为溶剂， 反应 8.8h， 生成
  参考文献：
  名称：

  Discovery of Hepatitis C Virus NS3-4A Protease Inhibitors with Improved Barrier to Resistance and Favorable Liver Distribution

  摘要：

  Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly Unproved potency against the key resistant variants and with increased liver partitioning.

  DOI：

  10.1021/jm400121t
• 作为产物：
  描述：

  氰乙酸乙酯 在 盐酸 作用下， 以 乙醚 、 异丙醇 为溶剂， 反应 24.25h， 生成 ethyl 3-methoxy-3-((3-methoxy-2-methylphenyl)imino)propanoate
  参考文献：
  名称：

  Discovery of Hepatitis C Virus NS3-4A Protease Inhibitors with Improved Barrier to Resistance and Favorable Liver Distribution

  摘要：

  Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly Unproved potency against the key resistant variants and with increased liver partitioning.

  DOI：

  10.1021/jm400121t