Estrogen receptor binding and estrogenic/antiestrogenic effects of two new metabolites of nitromiphene, 2-[p-[2-nitro-1-(4-methoxyphenyl)-2-phenylvinyl]phenoxy]-N-ethylpyrrolidine.
Reduction of the triarylethylene antiestrogen 2-[p-[2-nitro-1-(4-methoxphenyl)-2-phenylvinyl]phenoxy]-N-ethylpyrrolidine (1) with sodium borohydride-stannous chloride afforded 2-(p-methoxyphenyl)-p'-(2-pyrrolidin-1-ylethoxy)deoxybenzoin (2). Incubation of 1 with rat cecal content suspension under aerobic or anaerobic conditions also resulted in the generation of 2. The lactam analogue of 1 (6) was prepared by condensation of 4-(2-bromoethoxy)-4'-methoxybenzophenone (3) with benzylmagnesium chloride, followed by dehydration, amidation with 2-pyrrolidinone, and nitration. A metabolite with chromatographic and spectral properties identical with those of 6 was found in extracts from incubation mixtures of 1 with phenobarbital-induced rat liver 9000g supernatant. Compound 2 did not exhibit appreciable binding to the rat uterine cytosol estrogen receptor at concentrations of up to 1 X 10(-6) M and had no estrogenic or antiestrogenic activity in the 3-day rat uterotropic assay. By contrast, 6 had estrogen receptor affinity somewhat greater than that of 1 and slightly greater estrogenic activity accompanied by reduced antiestrogenic activity in comparison with those of 1.
D000818:Animals; D001711:Biotransformation; D002432:Cecum / Q000378:metabolism; D004965:Estrogen Antagonists / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D009594:Nitromifene / Q000031:analogs & derivatives / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
D004965:Estrogen Antagonists; D004967:Estrogens; D011759:Pyrrolidines; D011960:Receptors, Estrogen; D009594:Nitromifene; C039835:2-(4-methoxyphenyl)-4'-(2-(1-pyrrolidinyl)ethoxy)deoxybenzoin; C039836:2-(4-(2-nitro-1-(4-methoxyphenyl)-2-phenylvinyl)phenoxy)-N-ethylpyrrolidin-2-one