Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers

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Abstract

An effective epimerization of the normal estrone 3-methyl and 3-benzyl ethers by using o-phenylenediamine and AcOH made the possibility for facile entry into the 13α-estrone series. Combination of this synthetic methodology with an isolation step carried out by means of the Girard-P reagent, the corresponding ethers of 13-epi-estrone were obtained in excellent yields. The 3-hydroxy and 3-methoxy D-homoestrone derivatives in both the normal and the 13α-estrone series were then synthesized and tested in vitro in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities (RBAs) are lower than that of the reference compound 3,17β-estradiol. The progesterone receptor-binding affinities of the four D-homo derivatives were also tested showing low values for 13α-D-homoestrone and its 3-methyl ether. Pharmacologically, these 13α-D-homoestrone derivatives are estrogen receptor-selective molecules.

Original languageEnglish
Pages (from-to)277-288
Number of pages12
JournalSteroids
Volume68
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

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Methyl Ethers
Estrone
Ethers
Derivatives
Estrogen Receptors
Radioligand Assay
Progesterone Receptors
Estradiol
Assays
Molecules
D-homoestrone

Keywords

  • 13-epi-Estrone derivatives
  • D-Homosteroids
  • Estrogen receptor-binding

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

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title = "Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers",
abstract = "An effective epimerization of the normal estrone 3-methyl and 3-benzyl ethers by using o-phenylenediamine and AcOH made the possibility for facile entry into the 13α-estrone series. Combination of this synthetic methodology with an isolation step carried out by means of the Girard-P reagent, the corresponding ethers of 13-epi-estrone were obtained in excellent yields. The 3-hydroxy and 3-methoxy D-homoestrone derivatives in both the normal and the 13α-estrone series were then synthesized and tested in vitro in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities (RBAs) are lower than that of the reference compound 3,17β-estradiol. The progesterone receptor-binding affinities of the four D-homo derivatives were also tested showing low values for 13α-D-homoestrone and its 3-methyl ether. Pharmacologically, these 13α-D-homoestrone derivatives are estrogen receptor-selective molecules.",
keywords = "13-epi-Estrone derivatives, D-Homosteroids, Estrogen receptor-binding",
author = "J. W{\"o}lfling and E. Merny{\'a}k and E. Frank and G. Falkay and A. M{\'a}rki and Ren{\'a}ta Minorics and G. Schneider",
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T1 - Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers

AU - Wölfling, J.

AU - Mernyák, E.

AU - Frank, E.

AU - Falkay, G.

AU - Márki, A.

AU - Minorics, Renáta

AU - Schneider, G.

PY - 2003/3/1

Y1 - 2003/3/1

N2 - An effective epimerization of the normal estrone 3-methyl and 3-benzyl ethers by using o-phenylenediamine and AcOH made the possibility for facile entry into the 13α-estrone series. Combination of this synthetic methodology with an isolation step carried out by means of the Girard-P reagent, the corresponding ethers of 13-epi-estrone were obtained in excellent yields. The 3-hydroxy and 3-methoxy D-homoestrone derivatives in both the normal and the 13α-estrone series were then synthesized and tested in vitro in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities (RBAs) are lower than that of the reference compound 3,17β-estradiol. The progesterone receptor-binding affinities of the four D-homo derivatives were also tested showing low values for 13α-D-homoestrone and its 3-methyl ether. Pharmacologically, these 13α-D-homoestrone derivatives are estrogen receptor-selective molecules.

AB - An effective epimerization of the normal estrone 3-methyl and 3-benzyl ethers by using o-phenylenediamine and AcOH made the possibility for facile entry into the 13α-estrone series. Combination of this synthetic methodology with an isolation step carried out by means of the Girard-P reagent, the corresponding ethers of 13-epi-estrone were obtained in excellent yields. The 3-hydroxy and 3-methoxy D-homoestrone derivatives in both the normal and the 13α-estrone series were then synthesized and tested in vitro in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities (RBAs) are lower than that of the reference compound 3,17β-estradiol. The progesterone receptor-binding affinities of the four D-homo derivatives were also tested showing low values for 13α-D-homoestrone and its 3-methyl ether. Pharmacologically, these 13α-D-homoestrone derivatives are estrogen receptor-selective molecules.

KW - 13-epi-Estrone derivatives

KW - D-Homosteroids

KW - Estrogen receptor-binding

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