N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxopiperidine-3-carboxamide | 1612842-46-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxopiperidine-3-carboxamide
• 英文别名: N-[4-(2-amino-3-chloropyridin-4-yl)oxy-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopiperidine-3-carboxamide
• CAS: 1612842-46-2
• 化学式: C₂₃H₁₉ClF₂N₄O₃
• 分子量: 472.879
• InChiKey: CRXWIOHZDSNJQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,4-二氯吡啶 在 2,2,6,6-四甲基哌啶 、 4-二甲氨基吡啶 、 正丁基锂 、 碘苯二乙酸 、 potassium tert-butylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxopiperidine-3-carboxamide
  参考文献：
  名称：

  Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold

  摘要：

  一系列包含新型3-羧基哌啶-2-酮骨架的化合物基于引导结构BMS-777607进行设计、合成并评估其对c-Met激酶的抑制作用及对MKN45癌细胞系的细胞毒性。结果表明，五种化合物对c-Met展现出显著的抑制效果，IC50值为8.6−81 nM，而四种化合物对MKN45细胞增殖表现出强劲的抑制活性，IC50在0.57−16 μM之间。

  DOI：

  10.3390/molecules19022655

文献信息

• Discovery of novel type II c-Met inhibitors based on BMS-777607
  作者：Wei Zhang、Jing Ai、Dakuo Shi、Xia Peng、Yinchun Ji、Jian Liu、Meiyu Geng、Yingxia Li

  DOI：10.1016/j.ejmech.2014.04.056

  日期：2014.6

  Twenty-two new analogs based on the structure of BMS-777607 were designed, synthesized, and evaluated to determine their biological activities. Compounds bearing a cyclic sulfonamide or α-chloropiperidone scaffold exhibited good activity, which may provide a new basis for further structural optimization. Quinoline-containing analogs exhibited better results than did their counterparts with an aminopyrimidine, aminopyridine, or pyrrolopyridine unit. Two analogs, 22d and 22e, stood out as the most potent c-Met inhibitors with IC50s of 0.9 and 1.7 nM, respectively. These two compounds were more potent than BMS-777607 in enzymatic inhibition and cell proliferation studies.
• Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold
  作者：Wei Zhang、Jing Ai、Dakuo Shi、Xia Peng、Yinchun Ji、Jian Liu、Meiyu Geng、Yingxia Li

  DOI：10.3390/molecules19022655

  日期：——

  A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6−81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.57−16 μM.

  一系列包含新型3-羧基哌啶-2-酮骨架的化合物基于引导结构BMS-777607进行设计、合成并评估其对c-Met激酶的抑制作用及对MKN45癌细胞系的细胞毒性。结果表明，五种化合物对c-Met展现出显著的抑制效果，IC50值为8.6−81 nM，而四种化合物对MKN45细胞增殖表现出强劲的抑制活性，IC50在0.57−16 μM之间。