1-((1-((2-oxo-1,2-dihydroquinolin-4-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea | 1432579-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-((1-((2-oxo-1,2-dihydroquinolin-4-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea
• 英文别名: 1-[3-(chloromethyl)phenyl]-3-[[1-[(2-oxo-1H-quinolin-4-yl)methyl]triazol-4-yl]methyl]urea
• CAS: 1432579-00-4
• 化学式: C₂₁H₁₉ClN₆O₂
• 分子量: 422.874
• InChiKey: PEDSJHACZYVEDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(氯甲基)苯甲酸 在 叠氮磷酸二苯酯 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 叔丁醇 为溶剂， 反应 15.5h， 生成 1-((1-((2-oxo-1,2-dihydroquinolin-4-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea
  参考文献：
  名称：

  Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

  摘要：

  We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1,2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 mu M. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 mu M, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.042

文献信息

• Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach
  作者：Kingkan Sanphanya、Suvara K. Wattanapitayakul、Suwadee Phowichit、Valery V. Fokin、Opa Vajragupta

  DOI：10.1016/j.bmcl.2013.03.042

  日期：2013.5

  We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1,2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 mu M. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 mu M, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.