3-(4-bromophenyl)-1-(2-(2,4-difluorophenyl)-2-oxoethyl)-3-methylpyrrolidin-2-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(4-bromophenyl)-1-(2-(2,4-difluorophenyl)-2-oxoethyl)-3-methylpyrrolidin-2-one
• 英文别名: 3-(4-Bromophenyl)-1-[2-(2,4-difluorophenyl)-2-oxoethyl]-3-methylpyrrolidin-2-one；3-(4-bromophenyl)-1-[2-(2,4-difluorophenyl)-2-oxoethyl]-3-methylpyrrolidin-2-one
• 化学式: C₁₉H₁₆BrF₂NO₂
• 分子量: 408.242
• InChiKey: LNAVWIPLRWUOBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴苯乙酸甲酯 在 正丁基锂 、 cobalt(II) chloride hexahydrate 、 sodium hydride 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 mineral oil 为溶剂， 反应 0.83h， 生成 3-(4-bromophenyl)-1-(2-(2,4-difluorophenyl)-2-oxoethyl)-3-methylpyrrolidin-2-one
  参考文献：
  名称：

  Identification and Profiling of Hydantoins—A Novel Class of Potent Antimycobacterial DprE1 Inhibitors

  摘要：

  Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-beta-D-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.

  DOI：

  10.1021/acs.jmedchem.8b01356

文献信息

• Identification and Profiling of Hydantoins—A Novel Class of Potent Antimycobacterial DprE1 Inhibitors
  作者：Maciej K. Rogacki、Eleni Pitta、Olga Balabon、Sophie Huss、Eva Maria Lopez-Roman、Argyrides Argyrou、Delia Blanco-Ruano、Monica Cacho、Christophe M. L. Vande Velde、Koen Augustyns、Lluis Ballell、David Barros、Robert H. Bates、Fraser Cunningham、Pieter Van der Veken

  DOI：10.1021/acs.jmedchem.8b01356

  日期：2018.12.27

  Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-beta-D-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.