N⁴-(2-(1H-indol-3-yl)ethyl)-6-chloro-N²-(1H-indazol-5-yl)quinazoline-2,4-diamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N⁴-(2-(1H-indol-3-yl)ethyl)-6-chloro-N²-(1H-indazol-5-yl)quinazoline-2,4-diamine
• 英文别名: N4-(2-(1H-indol-3-yl)ethyl)-N2-(1H-indazol-5-yl)-6-chloroquinazoline-2,4-diamine；6-chloro-2-N-(1H-indazol-5-yl)-4-N-[2-(1H-indol-3-yl)ethyl]quinazoline-2,4-diamine
• 化学式: C₂₅H₂₀ClN₇
• 分子量: 453.934
• InChiKey: ASRZBBITPATROI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  94.3
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4,6-三氯喹唑啉 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 N⁴-(2-(1H-indol-3-yl)ethyl)-6-chloro-N²-(1H-indazol-5-yl)quinazoline-2,4-diamine
  参考文献：
  名称：

  Development of 2, 4-diaminoquinazoline derivatives as potent PAK4 inhibitors by the core refinement strategy

  摘要：

  Upon analysis of the reported crystal structure of PAK4 inhibitor KY04031 (PAK4 IC50 = 0.790 mu M) in the active site of PAK4, we investigated the possibility of changing the triazine core of KY04031 to a quinazoline. Using KY04031 as a starting compound, a library of 2, 4-diaminoquinazoline derivatives were designed and synthesized. These compounds were evaluated for PAK4 inhibition, leading to the identification of compound 9d (PAK4 IC50 = 0.033 mu M). Compound 9d significantly induced the cell cycle in the G1/S phase and inhibited migration and invasion of A549 cells that over-express PAK4 via regulation of the PAK4-LIMK1 signalling pathway. A docking study of compound 9d was performed to elucidate its possible binding modes and to provide a structural basis for further structure-guided design of PAK4 inhibitors. Compound 9d may serve as a lead compound for anticancer drug discovery and as a valuable research probe for further biological investigation of PAK4. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.02.063

文献信息

• Development of 2, 4-diaminoquinazoline derivatives as potent PAK4 inhibitors by the core refinement strategy
  作者：Chenzhou Hao、Wanxu Huang、Xiaodong Li、Jing Guo、Meng Chen、Zizheng Yan、Kai Wang、Xiaolin Jiang、Shuai Song、Jian Wang、Dongmei Zhao、Feng Li、Maosheng Cheng

  DOI：10.1016/j.ejmech.2017.02.063

  日期：2017.5

  Upon analysis of the reported crystal structure of PAK4 inhibitor KY04031 (PAK4 IC50 = 0.790 mu M) in the active site of PAK4, we investigated the possibility of changing the triazine core of KY04031 to a quinazoline. Using KY04031 as a starting compound, a library of 2, 4-diaminoquinazoline derivatives were designed and synthesized. These compounds were evaluated for PAK4 inhibition, leading to the identification of compound 9d (PAK4 IC50 = 0.033 mu M). Compound 9d significantly induced the cell cycle in the G1/S phase and inhibited migration and invasion of A549 cells that over-express PAK4 via regulation of the PAK4-LIMK1 signalling pathway. A docking study of compound 9d was performed to elucidate its possible binding modes and to provide a structural basis for further structure-guided design of PAK4 inhibitors. Compound 9d may serve as a lead compound for anticancer drug discovery and as a valuable research probe for further biological investigation of PAK4. (C) 2017 Published by Elsevier Masson SAS.