Synthesis and biological evaluation of omega-homologues of prostaglandin E1.

ABSTRACT

The synthesis and biological activities of some compounds with novel modifications of the omega side chain of prostaglandin E1 (PGE1) are described. The preparation of (+/-)-omega-Me-PGE1 (3) (+/-)-omega-Pr-PGE1 (5), and (+/-)-omega-Bu-PGE1 (6) is outlined. The compounds were evaluated for in vitro smooth muscle stimulating activity on isolated gerbil colon preparations, for hypotensive action in anesthetized rats, and for gastric antisecretory effects in histamine-stimulated Heidenhain pouch dogs. Structural changes in the omega position of the noncarboxyl side chain of PGE1 influenced the biological potency of the resulting compound when compared to the reference standard PGE1 (2). The homologues demonstrated interesting separation of biological activities; for example, 4 showed potent hypotensive activity (84% of PGE1, it showed very low smooth muscle stimulating activity. Compound 3 possessed the same order of potency as 2 in the gastric antisecretory assay.