N-[(5-chloro-8-hydroxyquinolin-7-yl)thiophen-2-ylmethyl]propanamide | 332939-67-0

• 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)thiophen-2-ylmethyl]propanamide
• 英文别名: N-((5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl)propionamide；N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]propanamide
• CAS: 332939-67-0
• 化学式: C₁₇H₁₅ClN₂O₂S
• 分子量: 346.837
• InChiKey: YTYAAHOPRAVKJV-UHFFFAOYSA-N

物化性质

• 沸点：
  621.4±55.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  90.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[(5-chloro-8-hydroxyquinolin-7-yl)thiophen-2-ylmethyl]propanamide 在 Chiralcel OD 作用下， 以 甲醇 为溶剂， 生成 (+)-N-((5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl)propionamide 、 (+)-N-((5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl)propionamide
  参考文献：
  名称：

  [EN] INHIBITORS OF HUMAN 12-LIPOXYGENASE
  [FR] INHIBITEURS DE LA 12-LIPOXYGÉNASE HUMAINE

  摘要：

  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。

  公开号：

  WO2011146618A1
• 作为产物：
  描述：

  2-噻吩甲醛 、 5-氯-8-羟基喹啉 、 丙酰胺 生成 N-[(5-chloro-8-hydroxyquinolin-7-yl)thiophen-2-ylmethyl]propanamide
  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

• Small molecule activators of mitochondrial function
  申请人：THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US10745390B2

  公开（公告）日：2020-08-18

  Methods for improving mitochondrial function, decreasing iron accumulation, and/or decreasing oxidative stress by exposing cells or treating a subject to compounds or compositions of the general formula are described that are beneficial in treating, for example, diseases and conditions such as Friedreich's ataxia, normal aging, and various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Furthermore, such compounds are useful as probes for identifying defects in mitochondrial metabolism, mitochondrial iron accumulation, cellular stress among other mitochondrial diseases and helping to identify compounds active in overcoming such defects.

  通过使细胞或治疗对象接触通式化合物或组合物来改善线粒体功能、减少铁积累和/或降低氧化应激的方法 所述方法有益于治疗例如弗里德雷氏共济失调、正常衰老以及阿尔茨海默病和帕金森病等各种神经退行性疾病。此外，这类化合物还可作为探针，用于鉴定线粒体代谢、线粒体铁积累、细胞应激等线粒体疾病的缺陷，并帮助鉴定对克服这些缺陷具有活性的化合物。
• 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
• SMALL MOLECULE ACTIVATORS OF MITOCHONDRIAL FUNCTION
  申请人：Wilson Robert B.

  公开号：US20120041023A1

  公开（公告）日：2012-02-16

  Methods for improving mitochondrial function, decreasing iron accumulation, and/or decreasing oxidative stress by exposing cells or treating a subject to compounds or compositions of the general formula (I) are described that are beneficial in treating, for example, diseases and conditions such as Friedreich's ataxia, normal aging, and various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Furthermore, such compounds are useful as probes for identifying defects in mitochondrial metabolism, mitochondrial iron accumulation, cellular stress among other mitochondrial diseases and helping to identify compounds active in overcoming such defects.
• US9000009B2
  申请人：——

  公开号：US9000009B2

  公开（公告）日：2015-04-07
• US9695157B2
  申请人：——

  公开号：US9695157B2

  公开（公告）日：2017-07-04