CHEMISTRY AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF C-17 UNSATURATED 18-CYCLOALKYL AND CYCLOALKENYL ANALOGS OF ENISOPROST - IDENTIFICATION OF A PROMISING NEW ANTIULCER PROSTAGLANDIN

被引：14

作者：

COLLINS, PW ^{[1
]}

GASIECKI, AF ^{[1
]}

PERKINS, WE ^{[1
]}

GULLIKSON, GW ^{[1
]}

BIANCHI, RG ^{[1
]}

KRAMER, SW ^{[1
]}

NG, JS ^{[1
]}

YONAN, EE ^{[1
]}

SWENTON, L ^{[1
]}

JONES, PH ^{[1
]}

BAUER, RF ^{[1
]}

机构：

[1] GD SEARLE & CO,DEPT PHYS METHODOL & CHEM DEV,SKOKIE,IL 60077

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 10期

关键词：

D O I：

10.1021/jm00172a017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of A17unsaturated cycloalkyl and cycloalkenyl analogues of enisoprost was synthesized to investigate the effects of ω 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 ω chain, and these chemical features impart some interesting oxidative and acid-catalyzed epimerization and allylic rearrangement reactivities, respectively. © 1990, American Chemical Society. All rights reserved.

引用

页码：2784 / 2793

页数：10

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