Synthesis and gastric antisecretory properties of 15-deoxy-16-hydroxyprostaglandin E analogs

Abstract

The preparation and gastric antisecretory activity of a series of 15-deoxy-16-hydroxyprostaglandin analogs are described. Compounds were tested i.v. in histamine-stimulated Heidenhain pouch dogs in relation to the reference standards PGE1 [prostaglandin E1] and PGE1 methyl ester (PGE1ME). The parent compound of this seris, (.+-.)-15-deoxy-16.alpha.,.beta.-hydroxyprostaglandin E1 methyl ester (3) was apparently equipotent to the reference standard PGE1ME. Methylation at C-16 of 3 produced a compound 8 which was apparently 40 times more potent than PGE1. Addition of 2 methyl groups to 3 at C15 or C17 markedly reduced antisecretory action. The 16-ethyl analog of 3 showed reduced potency. Removal or epimerization of the C-11 hydroxy group of 8 reduced the activity. Hydrogenation or changing the stereochemistry of the 13,14 double bond from trans to cis decreased the activity. .omega.-Homologation of 8 or introduction of a cis-5,6 double bond did not affect the potency. Two compounds along with 8 appear to possess optimum gastric antisecretory effects in this series.