N¹-(3,5-difluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)-N³-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)urea

• 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: N¹-(3,5-difluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)-N³-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)urea
• 英文别名: 1-[3,5-Difluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]-3-[2-(2,6-difluorophenyl)-4-oxo-1,3-thiazolidin-3-yl]urea；1-[3,5-difluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]-3-[2-(2,6-difluorophenyl)-4-oxo-1,3-thiazolidin-3-yl]urea
• 化学式: C₃₄H₃₄F₄N₆O₅S
• 分子量: 714.741
• InChiKey: SBEOBDKHXVHVBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  50
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline 在 吡啶 、 盐酸 、 四氯化硫 、 铁粉 、 一水合肼 、 溶剂黄146 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 二氯甲烷 、 水 、 氯苯 、 异丙醇 为溶剂， 反应 19.0h， 生成 N¹-(3,5-difluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)-N³-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)urea
  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

文献信息

• 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
  作者：Baohui Qi、Ying Yang、Guowei Gong、Huan He、Xupeng Yue、Xin Xu、Yun Hu、Junming Li、Tao Chen、Xiaobing Wan、Anmian Zhang、Guobiao Zhou

  DOI：10.1016/j.ejmech.2018.11.057

  日期：2019.2

  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.