N-((5-chloro-8-hydroxyquinolin-7-yl)methyl)acetamide | 1222818-75-8

• 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: N-((5-chloro-8-hydroxyquinolin-7-yl)methyl)acetamide
• 英文别名: N-[(5-chloro-8-hydroxyquinolin-7-yl)methyl]acetamide
• CAS: 1222818-75-8
• 化学式: C₁₂H₁₁ClN₂O₂
• 分子量: 250.685
• InChiKey: KYOGKKDOUJDRRE-UHFFFAOYSA-N

物化性质

• 沸点：
  537.9±50.0 °C(Predicted)
• 密度：
  1.374±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  乙酰胺 、 聚合甲醛 、 5-氯-8-羟基喹啉 生成 N-((5-chloro-8-hydroxyquinolin-7-yl)methyl)acetamide
  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

文献信息

• Discovery of Potent and Selective Inhibitors of Human Platelet-Type 12- Lipoxygenase
  作者：Victor Kenyon、Ganesha Rai、Ajit Jadhav、Lena Schultz、Michelle Armstrong、J. Brian Jameson、Steven Perry、Netra Joshi、James M. Bougie、William Leister、David A. Taylor-Fishwick、Jerry L. Nadler、Michael Holinstat、Anton Simeonov、David J. Maloney、Theodore R. Holman

  DOI：10.1021/jm2005089

  日期：2011.8.11

  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.