N-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-4-p-tolylpicolinamide | 1491141-87-7

• 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-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-4-p-tolylpicolinamide
• 英文别名: N-[3-fluoro-4-[[6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]quinoline-4-yl]oxy]phenyl]-4-(4-methylphenyl)pyridine-2-carboxamide；N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]-4-(4-methylphenyl)pyridine-2-carboxamide
• CAS: 1491141-87-7
• 化学式: C₃₇H₃₈FN₅O₄
• 分子量: 635.738
• InChiKey: YEGSATWQBXVWBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl)ethanone 在 bis(triphenylphosphine)palladium(II) dichloride 、 铁粉 、 sodium carbonate 、 氯化铵 、 溶剂黄146 、 N,N-二异丙基乙胺 、 potassium iodide 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 二甲胺 、 氯苯 、 甲苯 、 乙腈 为溶剂， 反应 71.5h， 生成 N-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-4-p-tolylpicolinamide
  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

文献信息

• Design, synthesis, and structure–activity relationships of novel 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents
  作者：Qidong Tang、Yanfang Zhao、Xinming Du、Lian'e Chong、Ping Gong、Chun Guo

  DOI：10.1016/j.ejmech.2013.08.019

  日期：2013.11

  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.