Synthesis and gastric antisecretory properties of allenic 16-phenoxy-omega-tetranor prostaglandin E analogs

In order to improve the modest oral activity of PGE₂ as an inhibitor of gastric acid secretion, analogs were prepared and tested orally in histamine-challenged rats. Insertion of a double bond at C-4, resulting in the 4,5-allene analog of PGE₁, gave a small increase in activity. Introduction of the ω-tetranor-16-phenoxy lower sidechain, a modification know to enhance activity in the PGF series, gave an eight-fold increase in activity. The analog having both modifications (enprostil, ) showed a six hundred-fold increase in oral antisecretory activity over PGE₂, which may reflect a potentiation effect. Modification of enprostil at C-1 (various esters) and at C-11 (11-methyl, 11-deoxy) generally resulted in compounds of high activity while modifications at other sites generally resulted in significant reductions in activity.