Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers.
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 13alpha-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 13alpha-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 3,17beta-estradiol. The progesterone receptor-binding affinities of the four D-homo derivatives were also tested showing low values for 13alpha-D-homoestrone and its 3-methyl ether. Pharmacologically, these 13alpha-D-homoestrone derivatives are estrogen receptor-selective molecules.
Wölfling
János
J
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720, Szeged, Hungary.
Mernyák
Erzsébet
E
Frank
Eva
E
Falkay
George
G
Márki
Arpád
A
Minorics
Renáta
R
Schneider
Gyula
G
D001665:Binding Sites; D001667:Binding, Competitive; D002625:Chemistry, Organic / Q000379:methods; D004970:Estrone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism; D008024:Ligands; D011869:Radioligand Assay; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D013237:Stereoisomerism
D008024:Ligands; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004970:Estrone