ethyl 5-[2-[2,8-bis(trifluoromethyl)-4-quinolinyl]ethyl]-3-isoxazolecarboxylate | 1197932-55-0

• 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: ethyl 5-[2-[2,8-bis(trifluoromethyl)-4-quinolinyl]ethyl]-3-isoxazolecarboxylate
• 英文别名: Ethyl 5-[2-[2,8-bis(trifluoromethyl)-4-quinolyl]ethyl]isoxazole-3-carboxylate；ethyl 5-[2-[2,8-bis(trifluoromethyl)quinolin-4-yl]ethyl]-1,2-oxazole-3-carboxylate
• CAS: 1197932-55-0
• 化学式: C₁₉H₁₄F₆N₂O₃
• 分子量: 432.322
• InChiKey: CYVXVJKVZWZKPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  ethyl (E)-5-[2-[2,8-bis(trifluoromethyl)-4-quinolinyl]ethenyl]-3-isoxazolecarboxylate 在 5% Pd(II)/C(eggshell) 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 8.0h， 生成 ethyl 5-[2-[2,8-bis(trifluoromethyl)-4-quinolinyl]ethyl]-3-isoxazolecarboxylate
  参考文献：
  名称：

  From Serendipity to Rational Antituberculosis Drug Discovery of Mefloquine-Isoxazole Carboxylic Acid Esters

  摘要：

  Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported anti-tuberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this series, chemistry efforts were focused on the modification of the oxymethylene linker of compound 3 in the present study. Compound 9d with an alkene linker was found to be both more metabolically stable and more potent than compound 3, with a minimum inhibitory concentration (MIC) of 0.2 mu M and 2.6 mu M against replicating and nonreplicating Mycobaterium tuberculosis, respectively. These attributes make 9d ail interesting lead compound. A number of modifications were made to the structure of 9d, and it series of active Compounds were discovered. Although some neurotoxicity was observed at it high dosage, this new series was endowed with both improved in vitro anti-TB activity and metabolic stability in comparison to compound 3.

  DOI：

  10.1021/jm900340a