5-fluoro-4-(4-fluoro-2-(pyrrolidin-1-ylsulfonyl)phenyl)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)pyrimidin-2-amine | 1341200-61-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-fluoro-4-(4-fluoro-2-(pyrrolidin-1-ylsulfonyl)phenyl)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)pyrimidin-2-amine
• 英文别名: 2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-N,N-dimethylbenzenesulfonamide
• CAS: 1341200-61-0
• 化学式: C₂₃H₂₈ClN₇O₂S
• 分子量: 502.04
• InChiKey: DUVYKNYFBDYPNC-UHFFFAOYSA-N

物化性质

• 沸点：
  676.9±65.0 °C(Predicted)
• 密度：
  1.361±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(4-甲基哌嗪)苯胺 、 2-((2,5-dichloropyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 叔丁醇 为溶剂， 反应 12.0h， 以24%的产率得到5-fluoro-4-(4-fluoro-2-(pyrrolidin-1-ylsulfonyl)phenyl)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)pyrimidin-2-amine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors

  摘要：

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.

  DOI：

  10.1021/ml200198x

文献信息

• Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors
  作者：Alexis Mollard、Steven L. Warner、Lee T. Call、Mark L. Wade、Jared J. Bearss、Anupam Verma、Sunil Sharma、Hariprasad Vankayalapati、David J. Bearss

  DOI：10.1021/ml200198x

  日期：2011.12.8

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.