4-chloro-N-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)picolinamide | 1491141-82-2

• 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: 4-chloro-N-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)picolinamide
• CAS: 1491141-82-2
• 化学式: C₃₀H₃₁ClFN₅O₄
• 分子量: 580.059
• InChiKey: IVIDNNCTHPPEGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.49
• 重原子数：
  41.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  89.05
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-chloro-N-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)picolinamide 、 4-甲氧基苯硼酸 在 bis(triphenylphosphine)palladium(II) dichloride 、 sodium carbonate 、 potassium iodide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以61%的产率得到N-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-4-(4-methoxyphenyl)picolinamide
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of novel 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents

  摘要：

  Two series of quinoline derivatives bearing the pyridine/pyrimidine scaffold were synthesized, and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency, and compared to foretinib, the most promising analog 18b (c-Met half-maximal inhibitory concentration [IC50] = 1.39 nM) showed a 7.3-fold increase in activity against HT-29 cell line in vitro. Structure activity relationship studies indicated that regulation of the electron density on the pyridine/pyrimidine ring to a proper degree was a key factor in improving the antitumor activity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.019
• 作为产物：
  描述：

  2-吡啶甲酸 在 氯化亚砜 、 N,N-二异丙基乙胺 、 sodium bromide 作用下， 以 二氯甲烷 、 氯苯 为溶剂， 反应 28.0h， 生成 4-chloro-N-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)picolinamide
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of novel 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents

  摘要：

  Two series of quinoline derivatives bearing the pyridine/pyrimidine scaffold were synthesized, and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency, and compared to foretinib, the most promising analog 18b (c-Met half-maximal inhibitory concentration [IC50] = 1.39 nM) showed a 7.3-fold increase in activity against HT-29 cell line in vitro. Structure activity relationship studies indicated that regulation of the electron density on the pyridine/pyrimidine ring to a proper degree was a key factor in improving the antitumor activity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.019