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
- 1 December 1983
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 26 (12), 1701-1705
- https://doi.org/10.1021/jm00366a008
Abstract
Reduction of the triarylethylene antiestrogen 2-[p-[2-nitro-1-(4-methoxphenyl)-2-phenylvinyl]phenoxy]-N-ethylpyrrolidine (1) with sodium borohydrate-stannous chloride afforded 2-(p-methoxyphenyl)-p''-(2-pyrrolidin-1-yl-ethoxy)deoxybenzoin (2). Incubation of 1 with rat cecal content suspension under aerobic or anaerobic conditions also resulted in the generation of 2. The lactam analog of 1 (6) was prepared by condensation of 4-(2-bromoethoxy)-4''-methoxybenzophenone 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 .times. 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.This publication has 19 references indexed in Scilit:
- High-affinity anti-oestrogen binding site distinct from the oestrogen receptorNature, 1980
- Antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,1,2,2-tetraalkyl-1,2-diphenylethanesJournal of Medicinal Chemistry, 1980
- Uterine bioassay of tamoxifen, trioxifene and a new estrogen antagonist (LY117018) in rats and miceLife Sciences, 1980
- Synthesis and antiestrogenic activity of [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]phenyl]methanone, methanesulfonic acid saltJournal of Medicinal Chemistry, 1979
- Anti-estrogen interaction with uterine estrogen receptors. Studies with a radiolabeled anti-estrogen (CI-628).Journal of Biological Chemistry, 1978
- A MONOHYDROXYLATED METABOLITE OF TAMOXIFEN WITH POTENT ANTIOESTROGENIC ACTIVITYJournal of Endocrinology, 1977
- A Comparative Study of Antiestrogen Action: Temporal Patterns of Antagonism of Estrogen Stimulated Uterine Growth and Effects on Estrogen Receptor Levels123Endocrinology, 1977
- ENZYMATIC PATHWAY FOR THE FORMATION OF COTININE, A MAJOR METABOLITE OF NICOTINE IN RABBIT LIVER1960
- The inhibition of organic nitro reductase by aureomycin in cell-free extracts. II. Cofactor requirements for the nitro reductase enzyme complexArchives of Biochemistry and Biophysics, 1954
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTJournal of Biological Chemistry, 1951