Synthesis and antifertility activity of omega-chain phenyl- and 16-phenoxy-analogues of (+/-)-11-deoxyprostaglandin F1 alpha.
Some omega-chain phenyl- and 16-phenoxy- analogues of (+/-)-11-deoxyprostaglandin F1 alpha have been synthesized and evaluated for anti-fertility activity in the hamster. 11-Deoxy-16-phenoxy-17,18,19,20-tetranor-PGF1 alpha was the most active member of the series with an ED50 equal to that of PGF2 alpha. 11-Deoxy-17-phenyl-18,19,20-trinor-PGF1 alpha, which was one third as active as PGF2 alpha, 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 PGF2 alpha receptor. Some quantitative structure-activity data supporting this finding are presented.
D000818:Animals; D002417:Cattle; D003338:Corpus Luteum / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D008186:Luteolytic Agents; D008297:Male; D011247:Pregnancy; D011461:Prostaglandins F, Synthetic / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000378:metabolism; D013329:Structure-Activity Relationship
D008186:Luteolytic Agents; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; C025568:11-deoxyprostaglandin F1alpha; D006911:Hydroxyprostaglandin Dehydrogenases