4-氯-7-甲氧基-6-(3-吗啉-4-基-丙氧基)-喹啉-3-腈 | 214475-85-1

• 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-7-甲氧基-6-(3-吗啉-4-基-丙氧基)-喹啉-3-腈
• 英文名称: 4-chloro-7-methoxy-6-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile
• 英文别名: 4-chloro-7-methoxy-6-(3-morpholin-4-yl-propoxy)-3-quinolinecarbonitrile；4-Chloro-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile
• CAS: 214475-85-1
• 化学式: C₁₈H₂₀ClN₃O₃
• 分子量: 361.828
• InChiKey: YXMQNJNJBCRYFJ-UHFFFAOYSA-N

物化性质

• 沸点：
  544.6±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  67.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  双(1H-苯并三唑-5-胺)硫酸盐 、 4-氯-7-甲氧基-6-(3-吗啉-4-基-丙氧基)-喹啉-3-腈 以 1-乙氧基乙醇 为溶剂， 反应 0.5h， 生成 4-(3H-benzotriazol-6-ylamino)-7-methoxy-6-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile hydrochloride
  参考文献：
  名称：

  SUBSTITUTED 3-CYANOQUINOLINES AS PROTEIN TYROSINE KINASES INHIBITORS

  摘要：

  公开号：

  EP1117659B1
• 作为产物：
  描述：

  3-羟基-4-甲氧基苯甲酸 在 palladium on activated charcoal 正丁基锂 、 氯化亚砜 、 硫酸 、 氢气 、 硝酸 、 tri-n-butylammonium iodide 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 丁酮 为溶剂， 生成 4-氯-7-甲氧基-6-(3-吗啉-4-基-丙氧基)-喹啉-3-腈
  参考文献：
  名称：

  Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents

  摘要：

  The syntheses and biological evaluations of 4-anilinoquinoline-3-carbonitrile analogues of the three clinical lead 4-anilinoquinazolines Iressa(TM), Tarceva(TM), and CI-1033 are described. The EGFR and HER-2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB-569. Similar activities are observed between these two series. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00598-x

文献信息

• Synthesis and structure–activity relationship of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitriles as EGFR tyrosine kinase inhibitors
  作者：Madhavi Pannala、Sunil Kher、Norma Wilson、John Gaudette、Ila Sircar、Shao-Hui Zhang、Alexei Bakhirev、Guang Yang、Phoebe Yuen、Frank Gorcsan、Naoki Sakurai、Miguel Barbosa、Jie-Fei Cheng

  DOI：10.1016/j.bmcl.2007.07.071

  日期：2007.11

  Synthesis and structure-activity relationship of a series of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitrile derivatives as EGFR inhibitors is described. Compounds 29 and 30 showed potent in vitro inhibitory activity in the enzymatic assay as well as in the functional cellular assay. They are moderately selective against other types of tyrosine kinases. (c) 2007 Elsevier Ltd. All rights reserved.
• SUBSTITUTED 3-CYANO QUINOLINES
  申请人：Wyeth Holdings Corporation

  公开号：EP0973746B1

  公开（公告）日：2003-09-24
• 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.