(5Z,8S,9S,11R,12R,15R)-13-oxa-16-[3-(3-chlorophenoxy)propoxy]-9,11,15-trihydroxy-17,18,19,20-tetranor-5-prostenoic acid | 228729-64-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (5Z,8S,9S,11R,12R,15R)-13-oxa-16-[3-(3-chlorophenoxy)propoxy]-9,11,15-trihydroxy-17,18,19,20-tetranor-5-prostenoic acid
• 英文别名: (Z)-7-[(1S,2R,3R,5S)-2-[(2R)-3-(3-chlorophenoxy)-2-hydroxypropoxy]-3,5-dihydroxycyclopentyl]hept-5-enoic acid
• CAS: 228729-64-4
• 化学式: C₂₁H₂₉ClO₇
• 分子量: 428.91
• InChiKey: HKIVGBPAUZBIOJ-MSKGSUGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  isopropyl (5Z,9S,11R,15R)-13-oxa-16-[3-(3-chlorophenoxy)propoxy]-9,11,15-trihydroxy-17,18,19,20-tetranor-5-prostenoate 在 lithium hydroxide monohydrate 、 potassium dihydrogenphosphate 作用下， 以 甲醇 、 水 为溶剂， 以8 mg的产率得到(5Z,8S,9S,11R,12R,15R)-13-oxa-16-[3-(3-chlorophenoxy)propoxy]-9,11,15-trihydroxy-17,18,19,20-tetranor-5-prostenoic acid
  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

文献信息

• Discovery of 13-oxa prostaglandin analogs as antiglaucoma agents: Synthesis and biological activity
  作者：Zixia Feng、Mark R. Hellberg、Najam A. Sharif、Marsha A. McLaughlin、Gary W. Williams、Daniel Scott、Tony Wallace

  DOI：10.1016/j.bmc.2008.11.070

  日期：2009.1

  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.