Antiestrogen Basicity-Activity Relationships: A Comparison of the Estrogen Receptor Binding and Antiuterotrophic Potencies of Several Analogues of (Z)-1,2-Diphenyl-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-butene (Tamoxifen, Nolvadex) Having Altered Basicity

David W. Robertson, John A. Katzenellenbogen, James R. Hayes, Benita S Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

A series of N-substituted (Z)-1,2-diphenyl-1-[4-(2-aminoethoxy)phenyl]-1-butenes, analogues of the antiestrogen tamoxifen (Nolvadex), in which the side-chain basicity is varied over a wide range, has been prepared to probe the importance of basicity in evoking estrogen antagonism. All of the compounds, except the pyrrole analogue 14, were found to possess significant antiestrogenic activity in the rat, as measured by their ability to inhibit estrogen-induced uterine growth. This implies that in the tamoxifen series the level of side-chain basicity, at least in the Lowry-Brønsted sense, is not a determining factor in the estrogen antagonist potencies of these compounds.

Original languageEnglish (US)
Pages (from-to)167-171
Number of pages5
JournalJournal of Medicinal Chemistry
Volume25
Issue number2
DOIs
StatePublished - Jan 1 1982

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Estrogen Receptor Modulators
Tamoxifen
Estrogen Receptors
Estrogens
Estrogen Antagonists
Pyrroles
Growth
1-butene
diphenyl

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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title = "Antiestrogen Basicity-Activity Relationships: A Comparison of the Estrogen Receptor Binding and Antiuterotrophic Potencies of Several Analogues of (Z)-1,2-Diphenyl-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-butene (Tamoxifen, Nolvadex) Having Altered Basicity",
abstract = "A series of N-substituted (Z)-1,2-diphenyl-1-[4-(2-aminoethoxy)phenyl]-1-butenes, analogues of the antiestrogen tamoxifen (Nolvadex), in which the side-chain basicity is varied over a wide range, has been prepared to probe the importance of basicity in evoking estrogen antagonism. All of the compounds, except the pyrrole analogue 14, were found to possess significant antiestrogenic activity in the rat, as measured by their ability to inhibit estrogen-induced uterine growth. This implies that in the tamoxifen series the level of side-chain basicity, at least in the Lowry-Br{\o}nsted sense, is not a determining factor in the estrogen antagonist potencies of these compounds.",
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AU - Katzenellenbogen, Benita S

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