3,4,5-Trifluorobenzoic acid 4-[[5-(1-naphthalenyl)-1,3,4-oxadiazol-2-yl]thio]but-2-ynyl ester | 1222805-76-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3,4,5-Trifluorobenzoic acid 4-[[5-(1-naphthalenyl)-1,3,4-oxadiazol-2-yl]thio]but-2-ynyl ester
• 英文别名: 4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 3,4,5-trifluorobenzoate
• CAS: 1222805-76-6
• 化学式: C₂₃H₁₃F₃N₂O₃S
• 分子量: 454.429
• InChiKey: REAKASMONPHWMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  90.5
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(5-(naphthalen-1-yl)-1,3,4-oxadiazol-2-ylthio)but-2-yn-1-ol 、 3,4,5-三氟苯甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 3,4,5-Trifluorobenzoic acid 4-[[5-(1-naphthalenyl)-1,3,4-oxadiazol-2-yl]thio]but-2-ynyl ester
  参考文献：
  名称：

  Discovery of Potent and Selective Inhibitors of Human Reticulocyte 15-Lipoxygenase-1

  摘要：

  There are a variety of lipoxygenases in the human body (hLO), each having a distinct role in cellular biology. Human reticulocyte 15-lipoxygenase-1 (15-hLO-1), which catalyzes the dioxygenation of 1,4-cis,cis-pentadiene-containing polyunsaturated fatty acids, is implicated in a number of diseases including cancer, atherosclerosis, and neurodegenerative conditions. Despite the potential therapeutic relevance of this target, few inhibitors have been reported that are both potent and selective. To this end, we have employed a quantitative high-throughput (qHTS) screen against similar to 74000 small molecules in search of reticulocyte 15-hLO-1 selective inhibitors. This screen led to the discovery of a novel chemotype for 15-hLO-1 inhibition, which displays nM potency and is > 7500-fold selective against the related isozymes, 5-hLO, platelet 12-hLO, epithelial 15-hLO-2, ovine cyclooxygenase-1, and human cyclooxygenase-2. In addition, kinetic experiments were performed which indicate that this class of inhibitor is tight binding, reversible, and appears not to reduce the active-site ferric ion.

  DOI：

  10.1021/jm1008852

文献信息

• Discovery of Potent and Selective Inhibitors of Human Reticulocyte 15-Lipoxygenase-1
  作者：Ganesha Rai、Victor Kenyon、Ajit Jadhav、Lena Schultz、Michelle Armstrong、J. Brian Jameson、Eric Hoobler、William Leister、Anton Simeonov、Theodore R. Holman、David J. Maloney

  DOI：10.1021/jm1008852

  日期：2010.10.28

  There are a variety of lipoxygenases in the human body (hLO), each having a distinct role in cellular biology. Human reticulocyte 15-lipoxygenase-1 (15-hLO-1), which catalyzes the dioxygenation of 1,4-cis,cis-pentadiene-containing polyunsaturated fatty acids, is implicated in a number of diseases including cancer, atherosclerosis, and neurodegenerative conditions. Despite the potential therapeutic relevance of this target, few inhibitors have been reported that are both potent and selective. To this end, we have employed a quantitative high-throughput (qHTS) screen against similar to 74000 small molecules in search of reticulocyte 15-hLO-1 selective inhibitors. This screen led to the discovery of a novel chemotype for 15-hLO-1 inhibition, which displays nM potency and is > 7500-fold selective against the related isozymes, 5-hLO, platelet 12-hLO, epithelial 15-hLO-2, ovine cyclooxygenase-1, and human cyclooxygenase-2. In addition, kinetic experiments were performed which indicate that this class of inhibitor is tight binding, reversible, and appears not to reduce the active-site ferric ion.