STRUCTURE-ACTIVITY RELATIONSHIPS OF ESTROGENS, EFFECTS OF 14-DEHYDROGENATION AND AXIAL METHYL GROUPS AT C-7, C-9 AND C-11

Article abstract of DOI:10.1016/0039-128X(83)90054-5

Thirty compounds were evaluated in the rat for uterotropic effects, inhibition of gonadotropin release, and competitive displacement of (3H) estradiol-17β from uterine cytosolic preparations. 7α-Methylestradiol-17β was 150percent as active as estradiol-17β as an uterotropic agent.Estradiol-17β was the most active inhibitor of gonadotropin release. 11β-Methylestradiol-17β had 124percent of the activity of estradiol-17β in displacing (3H) estradiol-17β from the "estrogen receptor." The 9α-methyl group considerably decreased the potency of estrogens in any of the three assays.The 14-dehydromodification was advantageous only in the estradiol-17β 3-methyl ether series.Uterotropic activities and inhibition of gonadotropin release did not parallel.The best compound for inhibiting gonadotropin release, as compared to uterotropic activity, was estrone.The "estrogen receptor" assay data correlated fairly well with uterotropic assay data, but only for compounds having free 3-hydroxyl groups; even so, some exceptions were noted.