(4-(4-(3-amino-1H-indazol-6-yl)benzoyl)piperazin-1-yl)(4-(dimethylamino)phenyl)methanone

• 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: (4-(4-(3-amino-1H-indazol-6-yl)benzoyl)piperazin-1-yl)(4-(dimethylamino)phenyl)methanone
• 英文别名: [4-(3-amino-1H-indazol-6-yl)phenyl]-[4-[4-(dimethylamino)benzoyl]piperazin-1-yl]methanone
• 化学式: C₂₇H₂₈N₆O₂
• 分子量: 468.558
• InChiKey: OHAKLBJQRKYWCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  98.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氟-4-溴苯腈 在 四(三苯基膦)钯 、 caesium carbonate 、 一水合肼 作用下， 以 水 、 乙腈 、 正丁醇 为溶剂， 反应 28.0h， 生成 (4-(4-(3-amino-1H-indazol-6-yl)benzoyl)piperazin-1-yl)(4-(dimethylamino)phenyl)methanone
  参考文献：
  名称：

  Discovery of novel Bcr-AblT315I inhibitors with flexible linker. Part 1: Confirmation optimization of phenyl-1H-indazol-3-amine as hinge binding moiety

  摘要：

  As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-Abl(wT) and Bcr-Abl(T3151) in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-Abl(wT) and Bcr-Abl(T3151) kinases with IC50 of 0.043 mu M and 0.17 mu M, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 mu M and 5.42 mu M, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.091

文献信息

• Discovery of novel Bcr-AblT315I inhibitors with flexible linker. Part 1: Confirmation optimization of phenyl-1H-indazol-3-amine as hinge binding moiety
  作者：Xiaoyan Pan、Liyuan Liang、Ying Sun、Ru Si、Qingqing Zhang、Jin Wang、Jia Fu、Junjie Zhang、Jie Zhang

  DOI：10.1016/j.ejmech.2019.05.091

  日期：2019.9

  As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-Abl(wT) and Bcr-Abl(T3151) in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-Abl(wT) and Bcr-Abl(T3151) kinases with IC50 of 0.043 mu M and 0.17 mu M, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 mu M and 5.42 mu M, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.