4-chloro-7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinoline | 1061610-62-5

• 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-chloro-7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinoline
• 英文别名: 4-chloro-6-methoxy-7-(3-(4-ethylpiperazin-1-yl)propoxy)quinoline；4-chloro-7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinoline
• CAS: 1061610-62-5
• 化学式: C₁₉H₂₆ClN₃O₂
• 分子量: 363.887
• InChiKey: AREQDBNHULRQQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  37.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-chloro-7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinoline 在 盐酸 、 铁粉 作用下， 以 乙醇 、 水 、 氯苯 为溶剂， 反应 3.0h， 生成 4-((7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluoroaniline
  参考文献：
  名称：

  Discovery of N-(4-((7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-N-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)urea as a multi-tyrosine kinase inhibitor for drug-sensitive and drug-resistant cancers treatment

  摘要：

  A series of 21 novel N-1-(2-aryl-1,3-thiazolidin-4-one)-N-3-aryl urea derivatives based on the previously identified lead compound I were synthesized and biologically characterized. The most promising compound 19a was identified as a multi-tyrosine kinase inhibitor, including c-Met, Ron, c-Kit, AXL and IGF-1R, etc. The results of real-time live-cell imaging indicated that compound 19a showed improved cytotoxicity and anti-proliferative activity against HT-29 cancer cells in a time- and dose-dependent manner, with an efficacy that was significantly greater than Cabozantinib. Flow cytometry and western blot analysis demonstrated the fact that anticancer activity was closely related with cancer cell apoptosis and the blockade of the phosphorylation of c-Met and its downstream signaling ERK and Akt. Furthermore, compound 19a also displayed slightly stronger effects on HT-29 cancer cells migration than that of Cabozantinib. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.11.057
• 作为产物：
  描述：

  香草乙酮 在 硝酸 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 三氯氧磷 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 26.5h， 生成 4-chloro-7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinoline
  参考文献：
  名称：

  Discovery of thiazolidin-4-one urea analogues as novel multikinase inhibitors that potently inhibit FLT3 and VEGFR2

  摘要：

  A series of novel thiazolidine-4-one urea analogues were designed, synthesized and biologically evaluated. The structure-activity relationship (SAR) at several positions of the scaffolds was investigated and its binding mode was analyzed by molecular modeling studies. Compound 17b proved to be the most potent one, and IC50 values against A549 and HT-29 cancer cell lines were 0.65 mu M and 0.11 mu M, respectively. The results of kinase profile demonstrated that compound 17b is a multikinase inhibitor that potently inhibits FLT3 (IC50 = 8.6 nM) and VEGFR2 (IC50 = 18.7 nM). The results of real-time live-cell imaging indicated that compound 17b showed excellent cytotoxicity and anti-proliferative activity against HT-29 cancer cells in a time- and dose-dependent manner, which was significantly potent than that of Cabozantinib. In addition, in vitro antitumor activity was associated with inducing cancer cell apoptosis and suppression of cancer cell migration.

  DOI：

  10.1016/j.bmc.2019.03.049

文献信息

• Design, Synthesis, and Biological Evaluation of Potent c-Met Inhibitors
  作者：Noel D. D’Angelo、Steven F. Bellon、Shon K. Booker、Yuan Cheng、Angela Coxon、Celia Dominguez、Ingrid Fellows、Douglas Hoffman、Randall Hungate、Paula Kaplan-Lefko、Matthew R. Lee、Chun Li、Longbin Liu、Elizabeth Rainbeau、Paul J. Reider、Karen Rex、Aaron Siegmund、Yaxiong Sun、Andrew S. Tasker、Ning Xi、Shimin Xu、Yajing Yang、Yihong Zhang、Teresa L. Burgess、Isabelle Dussault、Tae-Seong Kim

  DOI：10.1021/jm8006189

  日期：2008.9.25

  c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor. Subsequent SAR studies identified 22 as a more potent analog, whereas an X-ray crystal structure of 7 bound to c-Met revealed an unexpected binding conformation. This latter finding led to the development of a new series that featured compounds that were more potent both in vitro and in vivo than 22 and also exhibited different binding conformations to c-Met. Novel c-Met inhibitors have been designed, developed, and found to be potent in vitro and in vivo.
• Identification of (S)-1-(2-(2,4-difluorophenyl)-4-oxothiazolidin-3-yl)-3-(4-((7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)urea as a potential anti-colorectal cancer agent
  作者：Baohui Qi、Fei Wang、Huan He、Mengmeng Fan、Liping Hu、Li Xiong、Guowei Gong、Shengmin Shi、Xiaomeng Song

  DOI：10.1016/j.ejmech.2022.114561

  日期：2022.9