N-[(5-chloro-8-hydroxyquinolin-7-yl)-(furan-2-yl)methyl]-4-methylbenzamide | 1314642-41-5

• 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: N-[(5-chloro-8-hydroxyquinolin-7-yl)-(furan-2-yl)methyl]-4-methylbenzamide
• CAS: 1314642-41-5
• 化学式: C₂₂H₁₇ClN₂O₃
• 分子量: 392.842
• InChiKey: XXNBRJIXWKVRNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  糠醛 、 5-氯-8-羟基喹啉 、 对甲苯酰胺 生成 N-[(5-chloro-8-hydroxyquinolin-7-yl)-(furan-2-yl)methyl]-4-methylbenzamide
  参考文献：
  名称：

  Discovery of Potent and Selective Inhibitors of Human Platelet-Type 12- Lipoxygenase

  摘要：

  We report the discovery of novel small molecule inhibitors of platelet-type 12-human lipoxygenase, which display nanomolar activity against the purified enzyme, using a quantitative high-throughput screen (qHTS) on a library of 153607 compounds. These compounds also exhibit excellent specificity, >50-fold selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity vs ovine cyclooxygenase-1 and human cyclooxygenase-2. Kinetic experiments indicate this chemotype is a noncompetitive inhibitor that does not reduce the active site iron. Moreover, chiral HPLC separation of two of the racemic lead molecules revealed a strong preference for the (-)-enantiomers (IC50 of 0.43 +/- 0.04 and 0.38 +/- 0.05 mu M) compared to the (+)-enantiomers (IC50 of >25 mu M for both), indicating a fine degree of selectivity in the active site due to chiral geometry. In addition, these compounds demonstrate efficacy in cellular models, which underscores their relevance to disease modification.

  DOI：

  10.1021/jm2005089