(E)-2-(5-fluoro-1-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methylene)-1H-inden-3-yl)acetic acid | 1361000-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-2-(5-fluoro-1-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methylene)-1H-inden-3-yl)acetic acid
• 英文别名: 2-[(3E)-6-fluoro-3-[[4-[4-(trifluoromethyl)phenyl]phenyl]methylidene]inden-1-yl]acetic acid
• CAS: 1361000-88-5
• 化学式: C₂₅H₁₆F₄O₂
• 分子量: 424.394
• InChiKey: FBJFBJSUIISFFM-WOJGMQOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E)-2-(1-(4-bromobenzylidene)-5-fluoro-1H-inden-3-yl)ethanoic acid 、 4-三氟甲基苯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 14.0h， 以41%的产率得到(E)-2-(5-fluoro-1-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methylene)-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