2-chloro-N-(4-(5-fluoro-2-(4-hydroxyphenylamino)pyrimidin-4-ylamino)phenyl)benzamide | 1158838-40-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-N-(4-(5-fluoro-2-(4-hydroxyphenylamino)pyrimidin-4-ylamino)phenyl)benzamide
• 英文别名: 2-Chloro-N-[4-({5-Fluoro-2-[(4-Hydroxyphenyl)amino]pyrimidin-4-Yl}amino)phenyl]benzamide；2-chloro-N-[4-[[5-fluoro-2-(4-hydroxyanilino)pyrimidin-4-yl]amino]phenyl]benzamide
• CAS: 1158838-40-4
• 化学式: C₂₃H₁₇ClFN₅O₂
• 分子量: 449.872
• InChiKey: ZYURNHOEBWWJHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.2
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-chloro-N-(4-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)benzamide 、 对氨基苯酚 在 盐酸 作用下， 以 正丁醇 为溶剂， 反应 0.5h， 以77%的产率得到2-chloro-N-(4-(5-fluoro-2-(4-hydroxyphenylamino)pyrimidin-4-ylamino)phenyl)benzamide
  参考文献：
  名称：

  A Class of 2,4-Bisanilinopyrimidine Aurora A Inhibitors with Unusually High Selectivity against Aurora B

  摘要：

  The two major Aurora kinases carry out critical functions at distinct mitotic stages. Selective inhibitors of these kinases, as well as pan-Aurora inhibitors, show antitumor efficacy and are now under clinical investigation. However, the ATP-binding sites of Aurora A and Aurora B are virtually identical, and the structural basis for selective inhibition has therefore not been clear. We report here a class of bisanilinopyrimidine Aurora A inhibitors with excellent selectivity for Aurora A over Aurora B, both in enzymatic assays and in cellular phenotypic assays. Crystal structures of two of the inhibitors in complex with Aurora A implicate a single amino acid difference in Aurora B as responsible for poor inhibitory activity against this enzyme. Mutation of this residue in Aurora B (E161T) or Aurora A (T217E) is sufficient to swap the inhibition profile, suggesting that this difference might be exploited more generally to achieve high selectivity for Aurora A.

  DOI：

  10.1021/jm9000314

文献信息

• A Class of 2,4-Bisanilinopyrimidine Aurora A Inhibitors with Unusually High Selectivity against Aurora B
  作者：Ignacio Aliagas-Martin、Dan Burdick、Laura Corson、Jennafer Dotson、Jason Drummond、Carter Fields、Oscar W. Huang、Thomas Hunsaker、Tracy Kleinheinz、Elaine Krueger、Jun Liang、John Moffat、Gail Phillips、Rebecca Pulk、Thomas E. Rawson、Mark Ultsch、Leslie Walker、Christian Wiesmann、Birong Zhang、Bing-Yan Zhu、Andrea G. Cochran

  DOI：10.1021/jm9000314

  日期：2009.5.28

  The two major Aurora kinases carry out critical functions at distinct mitotic stages. Selective inhibitors of these kinases, as well as pan-Aurora inhibitors, show antitumor efficacy and are now under clinical investigation. However, the ATP-binding sites of Aurora A and Aurora B are virtually identical, and the structural basis for selective inhibition has therefore not been clear. We report here a class of bisanilinopyrimidine Aurora A inhibitors with excellent selectivity for Aurora A over Aurora B, both in enzymatic assays and in cellular phenotypic assays. Crystal structures of two of the inhibitors in complex with Aurora A implicate a single amino acid difference in Aurora B as responsible for poor inhibitory activity against this enzyme. Mutation of this residue in Aurora B (E161T) or Aurora A (T217E) is sufficient to swap the inhibition profile, suggesting that this difference might be exploited more generally to achieve high selectivity for Aurora A.