5-(4-aminophenyl)-4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)nicotinonitrile | 1436405-58-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-(4-aminophenyl)-4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)nicotinonitrile
• CAS: 1436405-58-1
• 化学式: C₂₅H₁₈ClFN₄O
• 分子量: 444.896
• InChiKey: QDIKNIDWEPHDDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.32
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  83.96
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-((4-methylpiperazin-1-yl)methyl)benzoyl chloride dihydrochloride 、 5-(4-aminophenyl)-4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)nicotinonitrile 在 吡啶 作用下， 反应 4.0h， 以39%的产率得到N-(4-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-5-cyanopyridin-3-yl)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors

  摘要：

  36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure-activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC50 value of 45 nM to EGFR kinase. Several compounds of other series also show IC50 values <1 mu M for EGFR and <5 mu M for A-549 and HL60 cells growth inhibition. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.053
• 作为产物：
  描述：

  1-(3,4-dimethoxybenzyl)-5-(4-nitrophenyl)-4-oxo-1,4-dihydropyridine-3-carbonitrile 在 盐酸 、 吡啶盐酸盐 、 铁粉 、 氯化铵 、 lithium chloride 、 三氯氧磷 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 9.0h， 生成 5-(4-aminophenyl)-4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)nicotinonitrile
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors

  摘要：

  36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure-activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC50 value of 45 nM to EGFR kinase. Several compounds of other series also show IC50 values <1 mu M for EGFR and <5 mu M for A-549 and HL60 cells growth inhibition. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.053