2-((6-methoxy-2-methylquinolin-4-yl)oxy)-N-(m-tolyl)acetamide

• 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-((6-methoxy-2-methylquinolin-4-yl)oxy)-N-(m-tolyl)acetamide
• 英文别名: 2-[(6-methoxy-2-methyl-4-quinolyl)oxy]-N-(m-tolyl)acetamide；2-(6-methoxy-2-methylquinolin-4-yl)oxy-N-(3-methylphenyl)acetamide
• 化学式: C₂₀H₂₀N₂O₃
• 分子量: 336.39
• InChiKey: ADCWQMHYOJDFMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  甲氧苯胺 在 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 3.0h， 生成 2-((6-methoxy-2-methylquinolin-4-yl)oxy)-N-(m-tolyl)acetamide
  参考文献：
  名称：

  Searching for New Leads for Tuberculosis: Design, Synthesis, and Biological Evaluation of Novel 2-Quinolin-4-yloxyacetamides

  摘要：

  In this study, a new series of more than 60 quinoline derivatives has been synthesized and evaluated against Mycobacterium tuberculosis (H37Rv). Apart from the SAR exploration around the initial hits, the optimization process focused on the improvement of the physicochemical properties, cytotoxicity, and metabolic stability of the series. The best compounds obtained exhibited MIC values in the low micromolar range, excellent intracellular antimycobacterial activity, and an improved physicochemical profile without cytotoxic effects. Further investigation revealed that the amide bond was the source for the poor blood stability observed, while some of the compounds exhibited hERG affinity. Compound 83 which contains a benzoxazole ring instead of the amide group was found to be a good alternative, with good blood stability and no hERG affinity, providing new opportunities for the series. Overall, the obtained results suggest that further optimization of solubility and microsomal stability of the series could provide a strong lead for a new anti-TB drug development program.

  DOI：

  10.1021/acs.jmedchem.6b00245