N-(3-fluoro-4-((2-((1-((methylsulfonyl)methyl)-1H-pyrazol-3-yl)amino)pyrimidin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide | 1584219-95-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-fluoro-4-((2-((1-((methylsulfonyl)methyl)-1H-pyrazol-3-yl)amino)pyrimidin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
• 英文别名: 1-N'-[3-fluoro-4-[2-[[1-(methylsulfonylmethyl)pyrazol-3-yl]amino]pyrimidin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
• CAS: 1584219-95-3
• 化学式: C₂₆H₂₃F₂N₇O₅S
• 分子量: 583.575
• InChiKey: ACUDHDKRSYSSKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  166
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1,1-环丙基二羧酸 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 N-(3-fluoro-4-((2-((1-((methylsulfonyl)methyl)-1H-pyrazol-3-yl)amino)pyrimidin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
  参考文献：
  名称：

  Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity

  摘要：

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.

  DOI：

  10.1021/ml500066m