4-Phenylamino 3-quinolinecarbonitrile deriv. 26

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-Phenylamino 3-quinolinecarbonitrile deriv. 26
• 英文别名: 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(2-morpholin-4-ylethoxy)quinoline-3-carbonitrile
• 化学式: C₂₄H₂₄Cl₂N₄O₄
• 分子量: 503.385
• InChiKey: LPZXIIKERBMSSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氯-7-羟基-6-甲氧基喹啉-3-甲腈 在 吡啶盐酸盐 、 三苯基膦 、 sodium iodide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙二醇乙醚 、 乙二醇二甲醚 为溶剂， 反应 4.25h， 生成 4-Phenylamino 3-quinolinecarbonitrile deriv. 26
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250

文献信息

• Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity
  作者：Diane H. Boschelli、Fei Ye、Yanong D. Wang、Minu Dutia、Steve L. Johnson、Biqi Wu、Karen Miller、Dennis W. Powell、Deanna Yaczko、Mairead Young、Mark Tischler、Kim Arndt、Carolyn Discafani、Carlo Etienne、Jay Gibbons、Janet Grod、Judy Lucas、Jennifer M. Weber、Frank Boschelli

  DOI：10.1021/jm0102250

  日期：2001.11.1

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.