2-chloro-N-(2-trifluoromethyl-1H-benzimidazol-5-yl)acetamide | 362594-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-chloro-N-(2-trifluoromethyl-1H-benzimidazol-5-yl)acetamide
• 英文别名: PCM-0102151；2-Chloro-N-(2-trifluoromethyl-1H-benzoimidazol-5-yl)-acetamide；2-chloro-N-[2-(trifluoromethyl)-3H-benzimidazol-5-yl]acetamide
• CAS: 362594-28-3
• 化学式: C₁₀H₇ClF₃N₃O
• mdl: MFCD00659924
• 分子量: 277.633
• InChiKey: JAAQGVSKJAZHKT-UHFFFAOYSA-N

物化性质

• 沸点：
  484.9±45.0 °C(Predicted)
• 密度：
  1.604±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为产物：
  描述：

  氯乙酰氯 、 5-氨基-2-(三氟甲基)苯并咪唑 以 N,N-二甲基乙酰胺 为溶剂， 以64%的产率得到2-chloro-N-(2-trifluoromethyl-1H-benzimidazol-5-yl)acetamide
  参考文献：
  名称：

  Discovery of Novel N-Phenylphenoxyacetamide Derivatives as EthR Inhibitors and Ethionamide Boosters by Combining High-Throughput Screening and Synthesis

  摘要：

  In this paper, we describe the screening of a 14640-compound library using a novel whole mycobacteria phenotypic assay to discover inhibitors of EthR, a transcriptional repressor implicated in the innate resistance of Mycobacterium tuberculosis to the second-line antituberculosis drug ethionamide. From this screening a new chemical family of EthR inhibitors bearing an N-phenylphenoxyacetamide motif was identified. The X-ray structure of the most potent compound crystallized with EthR inspired the synthesis of a 960-member focused library. These compounds were tested in vitro using a rapid thermal shift assay on EthR to accelerate the optimization. The best compounds were synthesized on a larger scale and confirmed as potent ethionamide boosters on M. tuberculosis-infected macrophages. Finally, the cocrystallization of the best optimized analogue with EthR revealed an unexpected reorientation of the ligand in the binding pocket.

  DOI：

  10.1021/jm300377g

文献信息

• Discovery of Novel <i>N</i>-Phenylphenoxyacetamide Derivatives as EthR Inhibitors and Ethionamide Boosters by Combining High-Throughput Screening and Synthesis
  作者：Marion Flipo、Nicolas Willand、Nathalie Lecat-Guillet、Candide Hounsou、Matthieu Desroses、Florence Leroux、Zoé Lens、Vincent Villeret、Alexandre Wohlkönig、René Wintjens、Thierry Christophe、Hee Kyoung Jeon、Camille Locht、Priscille Brodin、Alain R Baulard、Benoit Déprez

  DOI：10.1021/jm300377g

  日期：2012.7.26

  In this paper, we describe the screening of a 14640-compound library using a novel whole mycobacteria phenotypic assay to discover inhibitors of EthR, a transcriptional repressor implicated in the innate resistance of Mycobacterium tuberculosis to the second-line antituberculosis drug ethionamide. From this screening a new chemical family of EthR inhibitors bearing an N-phenylphenoxyacetamide motif was identified. The X-ray structure of the most potent compound crystallized with EthR inspired the synthesis of a 960-member focused library. These compounds were tested in vitro using a rapid thermal shift assay on EthR to accelerate the optimization. The best compounds were synthesized on a larger scale and confirmed as potent ethionamide boosters on M. tuberculosis-infected macrophages. Finally, the cocrystallization of the best optimized analogue with EthR revealed an unexpected reorientation of the ligand in the binding pocket.