2-chloro-N-(3-pyrimidin-5-yl-phenyl)acetamide | 1388657-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-N-(3-pyrimidin-5-yl-phenyl)acetamide
• 英文别名: 2-chloro-N-(3-pyrimidin-5-ylphenyl)acetamide
• CAS: 1388657-44-0
• 化学式: C₁₂H₁₀ClN₃O
• 分子量: 247.684
• InChiKey: HLGVMDOWUHEJQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  氯乙酰氯 、 3-嘧啶-5-苯胺 以 N,N-二甲基乙酰胺 为溶剂， 以51%的产率得到2-chloro-N-(3-pyrimidin-5-yl-phenyl)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