1-(2-{5-chloro-4-[2-(propane-2-sulfonyl)phenylamino]-2-ylamino}-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-6-yl)-2-hydroxy-ethanone

• 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: 1-(2-{5-chloro-4-[2-(propane-2-sulfonyl)phenylamino]-2-ylamino}-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-6-yl)-2-hydroxy-ethanone
• 英文别名: 1-[2-[[5-Chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl]-2-hydroxyethanone；1-[2-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl]-2-hydroxyethanone
• 化学式: C₂₂H₂₅ClN₆O₄S₂
• 分子量: 537.063
• InChiKey: NWGMBYQDXGHADH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  174
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,5-二氯-N-[2-[(1-甲基乙基)磺酰]苯基] 在 tris-(dibenzylideneacetone)dipalladium(0) 、 N-羟基-7-氮杂苯并三氮唑 、 1-氯乙基氯甲酸酯 、 potassium carbonate 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 4.0h， 生成 1-(2-{5-chloro-4-[2-(propane-2-sulfonyl)phenylamino]-2-ylamino}-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-6-yl)-2-hydroxy-ethanone
  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.