N-(1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl)acetamide | 1222395-08-5

• 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-(1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl)acetamide
• 英文别名: N-[1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl]acetamide
• CAS: 1222395-08-5
• 化学式: C₁₅H₁₇ClN₂O₂
• 分子量: 292.765
• InChiKey: UPWFKLQAXNTZLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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 、 5-氯-8-羟基喹啉 、 异丁醛 生成 N-(1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl)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

• [EN] INHIBITORS OF HUMAN 12-LIPOXYGENASE<br/>[FR] INHIBITEURS DE LA 12-LIPOXYGÉNASE HUMAINE
  申请人：US HEALTH

  公开号：WO2011146618A1

  公开（公告）日：2011-11-24

  Disclosed are inhibitors of human 12-lipoxygenase of Formula (I) or (II), wherein R1, R2, R3, and R4 are as defined herein, that are useful in treating or preventing a 12-lipoxygenase mediated disease or disorder, e.g., diabetes. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal.

  本发明涉及一种公式（I）或（II）的人类12-脂氧合酶抑制剂，其中R1、R2、R3和R4的定义如本文所述，该抑制剂可用于治疗或预防12-脂氧合酶介导的疾病或紊乱，例如糖尿病。本发明还涉及一种包含药学上可接受载体和至少一种本发明的抑制剂的组合物，以及一种用于治疗或预防哺乳动物中该疾病或紊乱的方法。
• INHIBITORS OF HUMAN 12-LIPOXYGENASE
  申请人：The U.S.A. as represented by the Secretary, Department of Health and Human Services

  公开号：EP2571853A1

  公开（公告）日：2013-03-27
• 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.