5-chlorocarbonyl-isoxazole-3-carboxylic acid ethyl ester | 1197932-08-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-chlorocarbonyl-isoxazole-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 5-carbonochloridoyl-1,2-oxazole-3-carboxylate
• CAS: 1197932-08-3
• 化学式: C₇H₆ClNO₄
• 分子量: 203.582
• InChiKey: FROKDLKLJAPHJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chlorocarbonyl-isoxazole-3-carboxylic acid ethyl ester 、 2,8-二(三氟甲基)-4-喹啉胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以50 mg的产率得到ethyl 5-[[(2,8-bis(trifluoromethyl)-4-quinolinyl)amino]carbonyl]-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
• 作为产物：
  描述：

  3-(ethoxycarbonyl)isoxazole-5-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 5-chlorocarbonyl-isoxazole-3-carboxylic acid ethyl ester
  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

文献信息

• From Serendipity to Rational Antituberculosis Drug Discovery of Mefloquine-Isoxazole Carboxylic Acid Esters
  作者：Jialin Mao、Hai Yuan、Yuehong Wang、Baojie Wan、Marco Pieroni、Qingqing Huang、Richard B. van Breemen、Alan P. Kozikowski、Scott G. Franzblau

  DOI：10.1021/jm900340a

  日期：2009.11.26

  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.