6β-[2-hydroxy-4-(3-trifluoromethylphenyl)butoxy]-7α-hydroxy-cis-2-oxabicyclo[3.3.0]-octan-3-one | 228729-62-2

• 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: 6β-[2-hydroxy-4-(3-trifluoromethylphenyl)butoxy]-7α-hydroxy-cis-2-oxabicyclo[3.3.0]-octan-3-one
• CAS: 228729-62-2
• 化学式: C₁₈H₂₁F₃O₅
• 分子量: 374.357
• InChiKey: SLZJQEIGIYGGPN-JKLZFGKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.08
• 重原子数：
  26.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  75.99
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3,4-二氢-2H-吡喃 、 6β-[2-hydroxy-4-(3-trifluoromethylphenyl)butoxy]-7α-hydroxy-cis-2-oxabicyclo[3.3.0]-octan-3-one 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以0.75 g的产率得到6β-[2-(tetrahydro-2H-pyran-2-yl)oxy-4-(3-trifluoromethylphenyl)butoxy]-7α-hydroxy-cis-2-oxabicyclo-[3.3.0]octan-3-one
  参考文献：
  名称：

  Discovery of 13-oxa prostaglandin analogs as antiglaucoma agents: Synthesis and biological activity

  摘要：

  FP-Class prostaglandin analogs have demonstrated utility for the treatment of glaucoma and ocular hypertension. A series of novel FP prostaglandin analogs was designed to optimize topical ocular activity and reduce ocular side-effects by replacing 13-carbon with oxygen. A facile synthesis was successfully developed for synthesis of the 13-oxa prostaglandins from the commercially available Corey aldehyde benzoate. Among the compounds synthesized, AL-16082 was the most potent prostaglandin FP agonist in vitro. In a prostaglandin FP receptor-linked second-messenger assay, phosphoinositide (PI) turnover, it exhibited a potency value (EC(50)) of 1.9 nM (78% max. response relative to. uprostenol). The isopropyl ester of AL-16082, compound AL-16049, significantly lowered intraocular pressure (IOP) in the ocular hypertensive monkey eyes by 30%. In the study of acute ocular irritation response in New Zealand albino rabbits, AL-16049 produced lower incidence of hyperemia, swelling, and discharge than PGF(2 alpha) (1 mu g), and a similar incidence of hyperemia, swelling, and discharge to latanoprost (1.8 mu g). AL-16049 also produced no signs of ocular irritation or discomfort in the cat at the doses evaluated. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.11.070
• 作为产物：
  描述：

  6β-glycidoxy-7α-benzoyloxy-cis-2-oxabicyclo[3.3.0]octan-3-one 、 (3-(trifluoromethyl)benzyl)magnesium bromide 在 copper(l) iodide 作用下， 以 乙醚 为溶剂， 反应 6.25h， 以0.56 g的产率得到6β-[2-hydroxy-4-(3-trifluoromethylphenyl)butoxy]-7α-hydroxy-cis-2-oxabicyclo[3.3.0]-octan-3-one
  参考文献：
  名称：

  Discovery of 13-oxa prostaglandin analogs as antiglaucoma agents: Synthesis and biological activity

  摘要：

  FP-Class prostaglandin analogs have demonstrated utility for the treatment of glaucoma and ocular hypertension. A series of novel FP prostaglandin analogs was designed to optimize topical ocular activity and reduce ocular side-effects by replacing 13-carbon with oxygen. A facile synthesis was successfully developed for synthesis of the 13-oxa prostaglandins from the commercially available Corey aldehyde benzoate. Among the compounds synthesized, AL-16082 was the most potent prostaglandin FP agonist in vitro. In a prostaglandin FP receptor-linked second-messenger assay, phosphoinositide (PI) turnover, it exhibited a potency value (EC(50)) of 1.9 nM (78% max. response relative to. uprostenol). The isopropyl ester of AL-16082, compound AL-16049, significantly lowered intraocular pressure (IOP) in the ocular hypertensive monkey eyes by 30%. In the study of acute ocular irritation response in New Zealand albino rabbits, AL-16049 produced lower incidence of hyperemia, swelling, and discharge than PGF(2 alpha) (1 mu g), and a similar incidence of hyperemia, swelling, and discharge to latanoprost (1.8 mu g). AL-16049 also produced no signs of ocular irritation or discomfort in the cat at the doses evaluated. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.11.070