18-Cycloalkyl Analogues of Enisoprost

Article abstract of DOI:10.1021/jm00125a013

By use of standard cuprate methodology, a series of 18-cycloalkyl analogues of enisoprost was prepared in an effort to impede ω chain metabolism and prolong duration of gastric antisecretory activity.An initial product of ω chain oxidation, the C-20 hydroxy analogue, was also synthesized for pharmacological comparison.The cyclopropyl, cyclobutyl, and cyclopentyl analogues were approximately one-fourth as potent as enisoprost in inhibiting gastric acid secretion, while the cyclohexyl and cycloheptyl analogues showed very weak activity, and the 20-hydroxy compound was inactive at a dose 100 times the ED 50 of enisoprost.The cyclobutyl compound had a longer duration of antisecretory action than enisoprost and the other cycloalkyl analogues.The cycloalkyl analogues unexpectedly possessed low diarrheogenic activity in rats.