N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)-amino)pyrimidin-2-yl)amino)phenyl)-1-(4-(dimethylamino)butanoyl)azetidine-3-carboxamide

• 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: N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)-amino)pyrimidin-2-yl)amino)phenyl)-1-(4-(dimethylamino)butanoyl)azetidine-3-carboxamide
• 英文别名: N-[3-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]-1-[4-(dimethylamino)butanoyl]azetidine-3-carboxamide
• 化学式: C₂₉H₃₆ClN₇O₄S
• 分子量: 614.168
• InChiKey: FYBQYJIHDABNSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(异丙基磺酰基)苯胺 在 palladium 10% on activated carbon 、 D(+)-10-樟脑磺酸 、 氢气 、 sodium hydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 3.0h， 生成 N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)-amino)pyrimidin-2-yl)amino)phenyl)-1-(4-(dimethylamino)butanoyl)azetidine-3-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