N-(3-(5-chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)-4-methoxyphenyl)-2-cyanoacetamide | 1453199-13-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(3-(5-chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)-4-methoxyphenyl)-2-cyanoacetamide
• 英文别名: N-[3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]-4-methoxyphenyl]-2-cyanoacetamide
• CAS: 1453199-13-7
• 化学式: C₂₂H₁₇ClN₆O₂
• 分子量: 432.869
• InChiKey: ONZWYLROLFHDPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-chloro-4-(1H-indol-3-yl)-N-(2-methoxy-5-nitrophenyl)pyrimidin-2-amine 在 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(3-(5-chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)-4-methoxyphenyl)-2-cyanoacetamide
  参考文献：
  名称：

  Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR)

  摘要：

  A novel series of small-molecule inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by molecular modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and demonstrates high levels of activity in cellular models of the double mutant form of EGFR. In addition, these compounds show significant activity against the activating mutations, which gefitinib and erlotinib target and inhibition of which gives rise to their observed clinical efficacy. A glutathione (GSH)-based assay was used to measure thiol reactivity toward the electrophilic functionality of the inhibitor series, enabling both the identification of a suitable reactivity window for their potency and the development of a reactivity quantitative structure-property relationship (QSPR) to support design.

  DOI：

  10.1021/jm400822z