2-(3-methoxyphenoxy)-N-(2-methylquinolin-6-yl)acetamide | 1388657-84-8

• 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: 2-(3-methoxyphenoxy)-N-(2-methylquinolin-6-yl)acetamide
• 英文别名: 2-(3-methoxyphenoxy)-N-(2-methyl-6-quinolyl)acetamide
• CAS: 1388657-84-8
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: WILZRTRWZZAFMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-氨基-2-甲基喹啉 在 potassium carbonate 作用下， 以 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 97.0h， 生成 2-(3-methoxyphenoxy)-N-(2-methylquinolin-6-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.