ethyl 2-(6-fluoro-1-hydroxy-2,3-dihydro-1H-inden-1-yl)-2-methylpropanoate | 1361000-76-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: ethyl 2-(6-fluoro-1-hydroxy-2,3-dihydro-1H-inden-1-yl)-2-methylpropanoate
• CAS: 1361000-76-1
• 化学式: C₁₅H₁₉FO₃
• 分子量: 266.312
• InChiKey: KNTYFYBJGGXELY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-(6-fluoro-1-hydroxy-2,3-dihydro-1H-inden-1-yl)-2-methylpropanoate 在 对甲苯磺酸 、 calcium chloride 、 sodium hydroxide 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 16.0h， 生成 (E)-ethyl 2-(5-fluoro-1-((4-methyl-2-phenylpyrimidin-5-yl)methylene)-1H-inden-3-yl)-2-methyl propanoate
  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
• 作为产物：
  描述：

  6-氟-1-茚酮 、 异丁酸乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 2.33h， 生成 ethyl 2-(6-fluoro-1-hydroxy-2,3-dihydro-1H-inden-1-yl)-2-methylpropanoate
  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