1-(4-fluorophenyl)-N-(3-fluoro-4-(6-(4-methoxybenzylamino)pyrimidin-4-yloxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

• 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: 1-(4-fluorophenyl)-N-(3-fluoro-4-(6-(4-methoxybenzylamino)pyrimidin-4-yloxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide
• 化学式: C₃₀H₂₃F₂N₅O₄
• 分子量: 555.541
• InChiKey: AKPIXZPWTSJIPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  41.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  107.37
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-N-(3-fluoro-4-(6-(4-methoxybenzylamino)pyrimidin-4-yloxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以68%的产率得到N-(4-(6-aminopyrimidin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  New aminopyrimidine derivatives as inhibitors of the TAM family

  摘要：

  In this study, we describe the synthesis of new pyrimidine analogs of BMS-777607, a potent and selective inhibitor of Met kinase. Inhibition of Met and Axl remained high whereas inhibition of Tyro3 and Mer decreased to some extend. The preferential moderate inhibition of the non-phosphorylated form of Abl1 of some derivatives suggests that they behave as type II inhibitors. This hypothesis was confirmed by docking studies into the structure of Met (3F82) and in a Tyro3 model where key interactions with the hinge region, the DFG-out motif and the allosteric pocket explain this inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.037
• 作为产物：
  描述：

  2-氟-4-硝基苯酚 在 氢气 、 potassium carbonate 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 1-(4-fluorophenyl)-N-(3-fluoro-4-(6-(4-methoxybenzylamino)pyrimidin-4-yloxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  New aminopyrimidine derivatives as inhibitors of the TAM family

  摘要：

  In this study, we describe the synthesis of new pyrimidine analogs of BMS-777607, a potent and selective inhibitor of Met kinase. Inhibition of Met and Axl remained high whereas inhibition of Tyro3 and Mer decreased to some extend. The preferential moderate inhibition of the non-phosphorylated form of Abl1 of some derivatives suggests that they behave as type II inhibitors. This hypothesis was confirmed by docking studies into the structure of Met (3F82) and in a Tyro3 model where key interactions with the hinge region, the DFG-out motif and the allosteric pocket explain this inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.037