5-chloro-N-{4-[(dimethylamino)methyl]-2-methoxy-5-nitrophenyl}-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine | 1453199-37-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-chloro-N-{4-[(dimethylamino)methyl]-2-methoxy-5-nitrophenyl}-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine
• CAS: 1453199-37-5
• 化学式: C₂₁H₂₀ClN₇O₃
• 分子量: 453.888
• InChiKey: XWMWOGKVKSWUQI-UHFFFAOYSA-N

物化性质

• 密度：
  1.43±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  110.72
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  5-chloro-N-{4-[(dimethylamino)methyl]-2-methoxy-5-nitrophenyl}-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine 在 palladium 10% on activated carbon 、 氢气 、 zinc(II) iodide 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 3.0h， 以66%的产率得到N1-(5-chloro-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl)-4-[(dimethylamino)methyl]-6-methoxybenzene-1,3-diamine
  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
• 作为产物：
  描述：

  (E)-4-(2-butoxyvinyl)-2,5-dichloropyrimidine 在 N-溴代丁二酰亚胺(NBS) 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.5h， 生成 5-chloro-N-{4-[(dimethylamino)methyl]-2-methoxy-5-nitrophenyl}-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine
  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