Synthesis and biologic activities of 11β-substituted estradiol as potential antiestrogens

Article abstract of DOI:10.1016/0039-128X(90)90022-4

The effect of attachment of a dimethylaminoethoxy or dimethylaminopropoxy group at the 11β-position of estradiol (E2) on its relative binding affinity (RBA) to estrogen receptor (ER) and intrinsic biologic activity is described.The binding of 11β-<2-(N,N-dimethylamino)ethoxy>estra-1,3,5(10)-triene-3,17β-diol (4) and 11β-<3-(N,N-dimethylamino)propoxy>estra-1,3,5(10)-triene-3,17β-diol (5) to the ER from the immature rat uterine tissue was measured relative to that of <3H>E2 by a competitive binding assay.It was found that the 11β-substituted E2 analogs have considerably lower RBA to ER than the corresponding parent compound.The intrinsic activity of compounds 4 and 5 were studied in terms of uterotrophic and antiuterotrophic activity.It was found that the uterotrophic activity of these compounds was drastically reduced compared with E2.However, no antiuterotrophic activity was observed in these compounds at dosages ranging from 1 to 100 μg/rat/d.