Synthesis and antifertility activity of ω-chain phenyl- and 16-phenoxy-analogues of (±)-11-deoxyprostaglandin F1α

Some ω-chain phenyl- and 16-phenoxy- analogues of (±)-11-deoxyprostaglandin F_1α have been synthesized and evaluated for anti-fertility activity in the hamster. 11-Deoxy-16-phenoxy-17,18,19,20-tetranor-PGF_1α was the most active member of the series with an ED₅₀ equal to that of PGF_2α. 11-Deoxy-17-phenyl-18,19,20-trinor-PGF_1α, which was one third as active as PGF_2α, was more potent than the corresponding 16- and 18-phenyl compounds. Aryl ring substitution was found to lower activity, except that with the 16-phenyl compound, p-bromo and m-trifluoromethyl substitution increased the potency.The antifertility activity of the phenoxy compounds, which were poor substrates for 15-hydroxyprostaglandin dehydrogenase, was shown to correlate well with the binding affinity for the bovine corpus luteum PGF_2α receptor. Some quantitative structure-activity data supporting this finding are presented.