4-(2-fluoro-4-nitrophenoxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine | 1584220-19-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2-fluoro-4-nitrophenoxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine
• CAS: 1584220-19-8
• 化学式: C₁₈H₁₅FN₄O₅S
• 分子量: 418.405
• InChiKey: DFMMHZCVERVHFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  124.32
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-(2-fluoro-4-nitrophenoxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以97%的产率得到4-(4-amino-2-fluorophenoxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine
  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
• 作为产物：
  描述：

  2-chloro-4-(2-fluoro-4-nitrophenoxy)pyrimidine 、 3-[(methylsulfonyl)methyl]aniline 在 对甲苯磺酸 作用下， 以 1,4-二氧六环 为溶剂， 以81%的产率得到4-(2-fluoro-4-nitrophenoxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine
  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