2-((2-((3-(2-aminoacetamido)phenyl)amino)-5-chloropyrimidin-4-yl)amino)-N-methylbenzamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-((2-((3-(2-aminoacetamido)phenyl)amino)-5-chloropyrimidin-4-yl)amino)-N-methylbenzamide
• 英文别名: 2-[[2-[3-[(2-aminoacetyl)amino]anilino]-5-chloropyrimidin-4-yl]amino]-N-methylbenzamide
• 化学式: C₂₀H₂₀ClN₇O₂
• 分子量: 425.877
• InChiKey: HBJCTXQIDBQUKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  134
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-((2-((3-(2-aminoacetamido)phenyl)amino)-5-chloropyrimidin-4-yl)amino)-N-methylbenzamide 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 pyrimidin-2-yl(amino)-N-(2-((3-(5-chloro-4-(2-(methylcarbamoyl)phenyl)amino)phenyl)amino)-2-oxoethyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases

  摘要：

  We have developed a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) bearing a flexible amino acid side chain, different from the majority of the literature reported ALK inhibitors that often possess a structurally constrained arylpiperazine fragment or its equivalents in the solvent-interaction region. Extensive structural elaboration led to compound 15 possessing IC50 values of 2.7 and 15.3 nM, respectively, in the ALK wild-type and gate-keeper mutant L1196M enzymatic assays. This compound not only showed high proliferative inhibition against ALK-addicted cells across different oncogenic forms but also effectively suppressed several ALK secondary mutant cells, including the gate-keeper L1196M and F1174L. Significant antitumor efficacy was achieved in the ALK-driven SUP-M2 xenograft model.

  DOI：

  10.1021/jm5005144
• 作为产物：
  描述：

  2-氨基-N-甲基苯甲酰胺 在 D(+)-10-樟脑磺酸 、 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 生成 2-((2-((3-(2-aminoacetamido)phenyl)amino)-5-chloropyrimidin-4-yl)amino)-N-methylbenzamide
  参考文献：
  名称：

  Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases

  摘要：

  We have developed a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) bearing a flexible amino acid side chain, different from the majority of the literature reported ALK inhibitors that often possess a structurally constrained arylpiperazine fragment or its equivalents in the solvent-interaction region. Extensive structural elaboration led to compound 15 possessing IC50 values of 2.7 and 15.3 nM, respectively, in the ALK wild-type and gate-keeper mutant L1196M enzymatic assays. This compound not only showed high proliferative inhibition against ALK-addicted cells across different oncogenic forms but also effectively suppressed several ALK secondary mutant cells, including the gate-keeper L1196M and F1174L. Significant antitumor efficacy was achieved in the ALK-driven SUP-M2 xenograft model.

  DOI：

  10.1021/jm5005144

文献信息

• Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases
  作者：Zilan Song、Yanhong Yang、Zhiqing Liu、Xia Peng、Junfeng Guo、Xinying Yang、Kui Wu、Jing Ai、Jian Ding、Meiyu Geng、Ao Zhang

  DOI：10.1021/jm5005144

  日期：2015.1.8

  We have developed a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) bearing a flexible amino acid side chain, different from the majority of the literature reported ALK inhibitors that often possess a structurally constrained arylpiperazine fragment or its equivalents in the solvent-interaction region. Extensive structural elaboration led to compound 15 possessing IC50 values of 2.7 and 15.3 nM, respectively, in the ALK wild-type and gate-keeper mutant L1196M enzymatic assays. This compound not only showed high proliferative inhibition against ALK-addicted cells across different oncogenic forms but also effectively suppressed several ALK secondary mutant cells, including the gate-keeper L1196M and F1174L. Significant antitumor efficacy was achieved in the ALK-driven SUP-M2 xenograft model.