4-氯-5,7-二甲氧基喹啉-3-甲腈 | 331662-73-8

• 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
• 中文名称: 4-氯-5,7-二甲氧基喹啉-3-甲腈
• 英文名称: 4-chloro-5,7-dimethoxy-3-quinolinecarbonitrile
• 英文别名: 4-Chloro-5,7-dimethoxyquinoline-3-carbonitrile
• CAS: 331662-73-8
• 化学式: C₁₂H₉ClN₂O₂
• mdl: MFCD09935343
• 分子量: 248.669
• InChiKey: RZOGZPVTDHUSRO-UHFFFAOYSA-N

物化性质

• 熔点：
  240-242 °C
• 沸点：
  425.2±40.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  55.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  2,4-二氯苯胺 、 4-氯-5,7-二甲氧基喹啉-3-甲腈 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以57%的产率得到3-Quinolinecarbonitrile deriv. 2g
  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
• 作为产物：
  描述：

  3,5-二甲氧基苯胺 在 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二苯醚 为溶剂， 反应 74.75h， 生成 4-氯-5,7-二甲氧基喹啉-3-甲腈
  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

• Synthesis and Structure–Activity Relationships of 3-Cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) Inhibitors
  作者：Nan Zhang、Biqi Wu、Dennis Powell、Allan Wissner、Middleton B. Floyd、Eleonora D. Kovacs、Lourdes Toral-Barza、Constance Kohler

  DOI：10.1016/s0960-894x(00)00580-1

  日期：2000.12

  A series of 3-cyano-4-(phenoxyanilino)cyanoquinolines has been prepared as MEK (MAP kinase kinase) inhibitors. The best activity is seen with alkoxy groups at both the 6- and 7-positions. The lead compounds show low nanomolar IC50's against MAP kinase kinase, and have potent inhibitory activity in tumor cells. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis and Src Kinase Inhibitory Activity of a Series of 4-Phenylamino-3-quinolinecarbonitriles
  作者：Diane H. Boschelli、Yanong D. Wang、Fei Ye、Biqi Wu、Nan Zhang、Minu Dutia、Dennis W. Powell、Allan Wissner、Kim Arndt、Jennifer M. Weber、Frank Boschelli

  DOI：10.1021/jm000420z

  日期：2001.3.1

  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.