7-Chloro-2-(4-chloro-phenyl)-6-methyl-quinoline-4-carbonyl chloride

• 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: 7-Chloro-2-(4-chloro-phenyl)-6-methyl-quinoline-4-carbonyl chloride
• 英文别名: 7-Chloro-2-(4-chlorophenyl)-6-methylquinoline-4-carbonyl chloride
• 化学式: C₁₇H₁₀Cl₃NO
• 分子量: 350.632
• InChiKey: QBXRHAPYOUSCES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-amino-N-(2,4-dimethoxybenzyloxy)-3-hydroxypropionamide 、 7-Chloro-2-(4-chloro-phenyl)-6-methyl-quinoline-4-carbonyl chloride 在 三乙胺 作用下， 以 吡啶 为溶剂， 反应 0.17h， 生成 7-Chloro-2-(4-chloro-phenyl)-6-methyl-quinoline-4-carboxylic acid [(R)-1-(2,4-dimethoxy-benzyloxycarbamoyl)-2-hydroxy-ethyl]-amide
  参考文献：
  名称：

  High-Throughput Catch-and-Release Synthesis of Oxazoline Hydroxamates. Structure−Activity Relationships in Novel Inhibitors of Escherichia coli LpxC:  In Vitro Enzyme Inhibition and Antibacterial Properties

  摘要：

  LpxC is a zinc amidase that catalyses the second step of lipid A biosynthesis in Gram-negative bacteria. Oxazolines incorporating a hydroxamic acid, which is believed to coordinate to the single essential zinc ion, at the 4-position are known inhibitors of this enzyme. Some of these enzyme inhibitors exhibit antibacterial activity through their inhibition of LpxC. We recently developed a method for the synthesis of oxazolines using resin capture and ring-forming release that eliminates traditional purification steps and can be used in high-throughput synthesis. Using our method, oxazoline hydroxamates with diverse 2-substituents were prepared in library form as candidate inhibitors for LpxC. Two conventional methods for oxazoline synthesis were also applied to generate more than 70 compounds. The groups at the 2-position included a wide variety of substituted aromatic rings and a limited selection of alkyl groups. These compounds were screened against wild-type and LpxC inhibitor-sensitive strains of Escherichia coli, as well as wildtype Pseudomonas aeruginosa. Inhibition of the E coli LpxC enzyme was also investigated. A broad correlation between enzyme inhibitory and antibacterial activity was observed, and novel compounds were discovered that exhibit antibacterial activity but fall outside earlier-known structural classes.

  DOI：

  10.1021/ja0209114