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

The effect of attachment of a dimethylaminoethoxy or a 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 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 μ/rat/d. (Steroids 55:238-241, 1990).