Estrogen and androgen receptor binding affinity of 10 beta-chloro-estrenen derivatives.
10 beta-Chloroestradien-3-one and its derivatives with chlorine substitution in ring A have been prepared. Efficient synthetic methods for 2-chloro- and 4-chloroestradiol are described. The binding affinity of these chlorinated estrogens to the uterine estrogen receptor was measured by a competitive binding assay using [3H]estradiol as ligand. 4-Chloroestradiol showed high binding affinity for the receptor (110% of that of estradiol). 2-Chloroestradiol, 10 beta-chloroestradien-3-one and 4,10 beta-dichloroestradien-3-one had moderate binding affinity. The structures of 10 beta-chloroestradien-3-one and androst-1,4-dien-3-one are very similar and can almost be superimposed. However, their binding affinities to the estrogen and androgen receptor were different. Androst-1,4-dien-3-one displayed no measurable affinity for the estrogen receptor and measurable affinity for the androgen receptor whereas 10 beta-chloroestradien-3-one had very low affinity for the androgen receptor.
Mukawa
F
F
Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
Suzuki
T
T
Ishibashi
M
M
Yamada
F
F
D000818:Animals; D001667:Binding, Competitive; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D004963:Estrenes / Q000138:chemical synthesis / Q000378:metabolism*; D008297:Male; D008958:Models, Molecular; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D014961:X-Ray Diffraction
C057956:10-chloroestradien-3-one; D004963:Estrenes; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D004958:Estradiol; C057955:2-chloroestradiol; C057954:4-chloroestradiol