(E)-2-(1-((6-(benzo[d][1,3]dioxol-5-yl)pyridin-2-yl)methylene)-5-fluoro-1H-inden-3-yl)acetic acid | 1361000-96-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (E)-2-(1-((6-(benzo[d][1,3]dioxol-5-yl)pyridin-2-yl)methylene)-5-fluoro-1H-inden-3-yl)acetic acid
• 英文别名: 2-[(3E)-3-[[6-(1,3-benzodioxol-5-yl)pyridin-2-yl]methylidene]-6-fluoroinden-1-yl]acetic acid
• CAS: 1361000-96-5
• 化学式: C₂₄H₁₆FNO₄
• 分子量: 401.394
• InChiKey: PMALRDGDORLEBX-OQLLNIDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-氟-1-茚酮 在 对甲苯磺酸 、 calcium chloride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 18.33h， 生成 (E)-2-(1-((6-(benzo[d][1,3]dioxol-5-yl)pyridin-2-yl)methylene)-5-fluoro-1H-inden-3-yl)acetic acid
  参考文献：
  名称：

  Cyclooxygenase-1-Selective Inhibitors Based on the (E)-2′-Des-methyl-sulindac Sulfide Scaffold

  摘要：

  Prostaglandins (PGs) are powerful lipid mediators in many physiological and pathophysiological responses. They are produced by oxidation of arachidonic acid (AA) by cyclo- oxygenases (COX-1 and COX-2) followed by metabolism of endoperoidde intermediates by terminal PG synthases. PG biosynthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs). Specific inhibition of COX-2 has been extensively investigated, but relatively few COX-1-selective inhibitors have been described. Recent reports of a possible contribution of COX-1 in analgesia, neuroinflammation, or carcinogenesis suggest that COX-1 is a potential therapeutic target. We designed, synthesized, and evaluated a series of (E)-2'-des-methyl-sulindac sulfide (E-DMSS) analogues for inhibition of COX-1. Several potent and selective inhibitors were discovered, and the most promising compounds were active against COX-1 in intact ovarian carcinoma cells (OVCAR-3). The compounds inhibited tumor cell proliferation but only at concentrations >100-fold higher than the concentrations that inhibit COX-1 activity. E-DMSS analogues may be useful probes of COX-1 biology in vivo and promising leads for COX-1-targeted therapeutic agents.

  DOI：

  10.1021/jm201528b

文献信息

• Cyclooxygenase-1-Selective Inhibitors Based on the (<i>E</i>)-2′-<i>Des</i>-methyl-sulindac Sulfide Scaffold
  作者：Andy J. Liedtke、Brenda C. Crews、Cristina M. Daniel、Anna L. Blobaum、Philip J. Kingsley、Kebreab Ghebreselasie、Lawrence J. Marnett

  DOI：10.1021/jm201528b

  日期：2012.3.8

  Prostaglandins (PGs) are powerful lipid mediators in many physiological and pathophysiological responses. They are produced by oxidation of arachidonic acid (AA) by cyclo- oxygenases (COX-1 and COX-2) followed by metabolism of endoperoidde intermediates by terminal PG synthases. PG biosynthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs). Specific inhibition of COX-2 has been extensively investigated, but relatively few COX-1-selective inhibitors have been described. Recent reports of a possible contribution of COX-1 in analgesia, neuroinflammation, or carcinogenesis suggest that COX-1 is a potential therapeutic target. We designed, synthesized, and evaluated a series of (E)-2'-des-methyl-sulindac sulfide (E-DMSS) analogues for inhibition of COX-1. Several potent and selective inhibitors were discovered, and the most promising compounds were active against COX-1 in intact ovarian carcinoma cells (OVCAR-3). The compounds inhibited tumor cell proliferation but only at concentrations >100-fold higher than the concentrations that inhibit COX-1 activity. E-DMSS analogues may be useful probes of COX-1 biology in vivo and promising leads for COX-1-targeted therapeutic agents.