Antiestrogens and Antiestrogen Metabolites: Preparation of Tritium-Labeled (±)-cis-3-[p-(1,2,3,4-Tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]-1,2-propanediol (U-23469) and Characterization and Synthesis of a Biologically Important Metabolite

Tochiro Tatee, Kathryn E. Carlson, John A. Katzenellenbogen, David W. Robertson, Benita S Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

The Upjohn antiestrogen (±)-cis-3-[p-(1, 2, 3, 4-tetrahydro-6-methoxy-2-phenyl-l-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-l, 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.

Original languageEnglish (US)
Pages (from-to)1509-1517
Number of pages9
JournalJournal of Medicinal Chemistry
Volume22
Issue number12
DOIs
StatePublished - Feb 1 1979

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Estrogen Receptor Modulators
Tritium
Estrogen Receptors
Propylene Glycols
Propylene Glycol
Alkylation
Palladium
Uterus
Gases
U 23469

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

@article{22d3cd79523f4ac1acd5c266ddca6fc2,
title = "Antiestrogens and Antiestrogen Metabolites: Preparation of Tritium-Labeled (±)-cis-3-[p-(1,2,3,4-Tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]-1,2-propanediol (U-23469) and Characterization and Synthesis of a Biologically Important Metabolite",
abstract = "The Upjohn antiestrogen (±)-cis-3-[p-(1, 2, 3, 4-tetrahydro-6-methoxy-2-phenyl-l-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-l, 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.",
author = "Tochiro Tatee and Carlson, {Kathryn E.} and Katzenellenbogen, {John A.} and Robertson, {David W.} and Katzenellenbogen, {Benita S}",
year = "1979",
month = "2",
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doi = "10.1021/jm00198a015",
language = "English (US)",
volume = "22",
pages = "1509--1517",
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TY - JOUR

T1 - Antiestrogens and Antiestrogen Metabolites

T2 - Preparation of Tritium-Labeled (±)-cis-3-[p-(1,2,3,4-Tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]-1,2-propanediol (U-23469) and Characterization and Synthesis of a Biologically Important Metabolite

AU - Tatee, Tochiro

AU - Carlson, Kathryn E.

AU - Katzenellenbogen, John A.

AU - Robertson, David W.

AU - Katzenellenbogen, Benita S

PY - 1979/2/1

Y1 - 1979/2/1

N2 - The Upjohn antiestrogen (±)-cis-3-[p-(1, 2, 3, 4-tetrahydro-6-methoxy-2-phenyl-l-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-l, 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.

AB - The Upjohn antiestrogen (±)-cis-3-[p-(1, 2, 3, 4-tetrahydro-6-methoxy-2-phenyl-l-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-l, 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.

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