(E)-N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)-amino)pyrimidin-2-yl)amino)phenyl)-2-(4-(4-(dimethylamino)but-2-enoyl)piperazin-1-yl)acetamide

• 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: (E)-N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)-amino)pyrimidin-2-yl)amino)phenyl)-2-(4-(4-(dimethylamino)but-2-enoyl)piperazin-1-yl)acetamide
• 英文别名: N-[3-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]-2-[4-[(E)-4-(dimethylamino)but-2-enoyl]piperazin-1-yl]acetamide
• 化学式: C₃₁H₃₉ClN₈O₄S
• 分子量: 655.221
• InChiKey: FJSAYHJPHADVOT-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  10

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 、 potassium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 (E)-N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)-amino)pyrimidin-2-yl)amino)phenyl)-2-(4-(4-(dimethylamino)but-2-enoyl)piperazin-1-yl)acetamide
  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