依尼前列素C-17位不饱和18-环烷基和环烯基类似物的化学及构效关系。一种有前景的新型抗溃疡前列腺素的鉴定。

Chemistry and structure-activity relationships of C-17 unsaturated 18-cycloalkyl and cycloalkenyl analogues of enisoprost. Identification of a promising new antiulcer prostaglandin.

作者信息

Collins P W, Gasiecki A F, Perkins W E, Gullikson G W, Bianchi R G, Kramer S W, Ng J S, Yonan E E, Swenton L, Jones P H

机构信息

Physical Methodology Department, G.D. Searle & Co., Skokie, Illinois 60077.

出版信息

J Med Chem. 1990 Oct;33(10):2784-93. doi: 10.1021/jm00172a017.

DOI:10.1021/jm00172a017

PMID:2213831

Abstract

A series of delta 17 unsaturated cycloalkyl and cycloalkenyl analogues of enisoprost was synthesized to investigate the effects of omega chain unsaturation on gastric antisecretory activity and diarrheogenic side effects. Of these, the 17E, 18-cyclopentenyl analogue 5d displayed potent gastric antisecretory activity in dogs but very weak diarrheogenic properties in rats and is the most selective prostaglandin compound discovered in these laboratories. Structurally, 5d contains both a conjugated diene and tertiary allylic alcohol in the omega chain, and these chemical features impart some interesting oxidative and acid-catalyzed epimerization and allylic rearrangement reactivities, respectively.

摘要

合成了一系列依尼前列素的δ17不饱和环烷基和环烯基类似物，以研究ω链不饱和对胃抗分泌活性和致腹泻副作用的影响。其中，17E，18-环戊烯基类似物5d在犬中显示出强效的胃抗分泌活性，但在大鼠中致腹泻特性非常弱，是在这些实验室中发现的最具选择性的前列腺素化合物。从结构上看，5d在ω链中同时含有共轭二烯和叔烯丙醇，这些化学特征分别赋予了一些有趣的氧化和酸催化的差向异构化以及烯丙基重排反应活性。