Antiestrogens and antiestrogen metabolites: preparation of tritium-labeled (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxyl]-1,2-propanediol (U-23469) and characterization and synthesis of a biologically important metabolite.

doi:10.1021/JM00198A015

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Antiestrogens and antiestrogen metabolites: preparation of tritium-labeled (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxyl]-1,2-propanediol (U-23469) and characterization and synthesis of a biologically important metabolite.

Published Dec 1, 1979 · T. Tatee, K. Carlson, J. Katzenellenbogen

Journal of medicinal chemistry

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28

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Abstract

The Upjohn antiestrogen (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]-1,2-propanediol (2b, U 23469) has been prepared in tritium-labeled form by reduction of an unsaturated dihydronaphthalene precursor with carrier-free tritium gas over a palladium catalyst followed by alkylation with 3-iodo-1,2-propanediol. After extensive chromatographic purification, the final material was obtained with a specific activity of 13 Ci/mmol and a radiochemical purity of 94%. In vivo studies with immature rats show that [3H]2b is slowly converted to a more polar metabolite that is selectively accumulated in the nuclear fraction of the uterus where it is bound to the estrogen receptor. Chromatographic comparisons indicate that this metabolite is the demethylated analogue 2c, a compound that has an affinity for estrogen receptor more than 300 times greater than that of 2b. These studies suggest that the demethylated analogue 2c may be a biologically important metabolite of 2b that is involved in the action of this antiestrogen.

In Vitro Study

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Key takeawayThe demethylated analogue 2c, with a 300-fold greater affinity for estrogen receptor, is a biologically important metabolite of the antiestrogen 2b, involved in its action.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Antiestrogens and antiestrogen metabolites: preparation of tritium-labeled (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxyl]-1,2-propanediol (U-23469) and characterization and synthesis of a biologically important metabolite.

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