N-[3-fluoro-5-(4-methylimidazol-1-yl)phenyl]-4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide | 1421681-18-6

• 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: N-[3-fluoro-5-(4-methylimidazol-1-yl)phenyl]-4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide
• CAS: 1421681-18-6
• 化学式: C₂₇H₂₂FN₇O
• 分子量: 479.516
• InChiKey: SDYGMEWQBSWSIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-氟-3-碘-5-硝基苯 在 copper(I) oxide 、 tin(II) chloride dihdyrate 、 4,7-二甲氧基-1,10-菲咯啉 、 caesium carbonate 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙腈 为溶剂， 生成 N-[3-fluoro-5-(4-methylimidazol-1-yl)phenyl]-4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide
  参考文献：
  名称：

  Synthesis and biological evaluation of analogues of the kinase inhibitor nilotinib as Abl and Kit inhibitors

  摘要：

  The importance of the trifluoromethyl group in the polypharmacological profile of nilotinib was investigated. Molecular editing of nilotinib led to the design, synthesis and biological evaluation of analogues where the trifluoromethyl group was replaced by a proton, fluorine and a methyl group. While these analogues were less active than nilotinib toward Abl, their activity toward Kit was comparable, with the monofluorinated analogue being the most active. Docking of nilotinib and of analogues 2a-c to the binding pocket of Abl and of Kit showed that the lack of shape complementarity in Kit is compensated by the stabilizing effect from its juxtamembrane region. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.11.111

文献信息

• Synthesis and biological evaluation of analogues of the kinase inhibitor nilotinib as Abl and Kit inhibitors
  作者：Damien Y. Duveau、Xin Hu、Martin J. Walsh、Suneet Shukla、Amanda P. Skoumbourdis、Matthew B. Boxer、Suresh V. Ambudkar、Min Shen、Craig J. Thomas

  DOI：10.1016/j.bmcl.2012.11.111

  日期：2013.2

  The importance of the trifluoromethyl group in the polypharmacological profile of nilotinib was investigated. Molecular editing of nilotinib led to the design, synthesis and biological evaluation of analogues where the trifluoromethyl group was replaced by a proton, fluorine and a methyl group. While these analogues were less active than nilotinib toward Abl, their activity toward Kit was comparable, with the monofluorinated analogue being the most active. Docking of nilotinib and of analogues 2a-c to the binding pocket of Abl and of Kit showed that the lack of shape complementarity in Kit is compensated by the stabilizing effect from its juxtamembrane region. Published by Elsevier Ltd.