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-dichloroanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
• 化学式: C₂₅H₂₇Cl₂N₅O₂
• 分子量: 500.428
• InChiKey: MVQUQGLRQPMJPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-7-(3-氯丙氧基)-3-氰基-6-甲氧基喹啉 在 吡啶盐酸盐 、 sodium iodide 作用下， 以 乙二醇乙醚 为溶剂， 反应 79.0h， 生成 4-Phenylamino-3-quinolinecarbonitrile deriv. 26
  参考文献：
  名称：

  Synthesis and Src Kinase Inhibitory Activity of a Series of 4-Phenylamino-3-quinolinecarbonitriles

  摘要：

  Screening of a directed compound library in a yeast-based assay identified 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (2a) as a Src inhibitor. An enzymatic assay established that 2a was an ATP-competitive inhibitor of the kinase activity of Src. We present here SAR data for 2a which shows that the aniline group at C-4, the carbonitrile group at C-3, and the alkoxy groups at C-6 and C-7 of the quinoline are crucial for optimal activity. Increasing the size of the C-2 substituent of the aniline at C-4 of 2a from chloro to bromo to iodo resulted in a corresponding increase in Src inhibition. Furthermore, replacement of the 7-methoxy group of 2a with various 3-heteroalkylaminopropoxy groups provided increased inhibition of both Src enzymatic and cellular activity. Compound 25, which contains a 3-morpholinopropoxy group, had an IC50 of 3.8 nM in the Src enzymatic assay and an IC50 of 940 nM for the inhibition of Src-dependent cell proliferation.

  DOI：

  10.1021/jm000420z

文献信息

• METHODS FOR TREATING ALZHEIMER'S DISEASE
  申请人：Lichter Jay

  公开号：US20120270844A1

  公开（公告）日：2012-10-25

  Provided herein arc PAK inhibitors. Also provided herein are compositions and methods for treating an individual suffering from Alzheimer's disease.

  本文提供了PAK抑制剂。同时还提供了治疗患有阿尔茨海默病个体的组合物和方法。
• METHODS FOR TREATING SCHIZOPHRENIA
  申请人：Lichter Jay

  公开号：US20120184547A1

  公开（公告）日：2012-07-19

  Provided herein are PAK inhibitors. Also provided herein are compositions and methods for treating an individual suffering from schizophrenia.

  提供PAK抑制剂。此外，还提供了用于治疗患有精神分裂症的个体的组合物和方法。
• METHODS FOR TREATING MILD COGNITIVE IMPAIRMENT
  申请人：Lichter Jay

  公开号：US20130059824A1

  公开（公告）日：2013-03-07

  Provided herein are PAK inhibitors. Also provided herein are compositions and methods for treating an individual suffering from Mild Cognitive Impairment.

  本文提供了PAK抑制剂。同时提供了治疗轻度认知障碍患者的组合物和方法。
• METHODS FOR TREATING AUTISM
  申请人：Lichter Jay

  公开号：US20130096115A1

  公开（公告）日：2013-04-18

  Provided herein are PAK inhibitors. Also provided herein are compositions and methods for treating an individual suffering from autism.

  本文提供PAK抑制剂。同时，本文还提供了治疗患有自闭症个体的组合物和方法。
• METHODS FOR TREATING NEUROLOGICAL CONDITIONS
  申请人：Lichter Jay

  公开号：US20130225575A1

  公开（公告）日：2013-08-29

  Provided herein are PAK inhibitors. Also provided herein are compositions and methods for treating an individual suffering from certain neurological conditions.

  本文提供了PAK抑制剂。同时提供了用于治疗患有某些神经疾病的个体的组合物和方法。