N-(3-bromophenyl)-N'-{2-chloro-4-[(thieno[2,3-d]pyrimidin-4-yl)oxy]phenyl}urea

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-bromophenyl)-N'-{2-chloro-4-[(thieno[2,3-d]pyrimidin-4-yl)oxy]phenyl}urea
• 英文别名: 1-(3-Bromophenyl)-3-(2-chloro-4-thieno[2,3-d]pyrimidin-4-yloxyphenyl)urea；1-(3-bromophenyl)-3-(2-chloro-4-thieno[2,3-d]pyrimidin-4-yloxyphenyl)urea
• 化学式: C₁₉H₁₂BrClN₄O₂S
• 分子量: 475.753
• InChiKey: BHCTVLPFBNCLFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯噻吩[2,3-D]嘧啶 、 N-(3-bromophenyl)-N'-(2-chloro-4-hydroxyphenyl)urea 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 丁酮 为溶剂， 反应 1.0h， 以11%的产率得到N-(3-bromophenyl)-N'-{2-chloro-4-[(thieno[2,3-d]pyrimidin-4-yl)oxy]phenyl}urea
  参考文献：
  名称：

  Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors

  摘要：

  Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmacological evaluation against nine kinases (EGFR, PDGFR-ss, c-Kit, c-Met, Src, Raf, VEGFR-1, -2 and -3). Most of the synthesized compounds showed from moderate to potent activities against c-Kit with IC50 values in the nanomolar range. Among them, 4-anilino(urea) thienopyrimidine analogs showed selectivity and potent c-Kit inhibition with IC50 values less than 6 nM. Docking simulation was performed for the most promising compound 9 into the c-Kit active site to determine the potential binding mode. This study reveal that the 4-anilino(urea) thienopyrimidine is an interesting scaffold to design novel potent and selective c-Kit inhibitors which may make promising candidates for cancers where c-Kit receptors are overexpressed. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.035

文献信息

• Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors
  作者：Séverine Ravez、Stéphane Arsenlis、Amélie Barczyk、Anthony Dupont、Raphaël Frédérick、Stéphanie Hesse、Gilbert Kirsch、Patrick Depreux、Laurence Goossens

  DOI：10.1016/j.bmc.2015.10.035

  日期：2015.11

  Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmacological evaluation against nine kinases (EGFR, PDGFR-ss, c-Kit, c-Met, Src, Raf, VEGFR-1, -2 and -3). Most of the synthesized compounds showed from moderate to potent activities against c-Kit with IC50 values in the nanomolar range. Among them, 4-anilino(urea) thienopyrimidine analogs showed selectivity and potent c-Kit inhibition with IC50 values less than 6 nM. Docking simulation was performed for the most promising compound 9 into the c-Kit active site to determine the potential binding mode. This study reveal that the 4-anilino(urea) thienopyrimidine is an interesting scaffold to design novel potent and selective c-Kit inhibitors which may make promising candidates for cancers where c-Kit receptors are overexpressed. (C) 2015 Elsevier Ltd. All rights reserved.