Structure-activity relationships of estrogens: effects of esterification of the 11 beta-hydroxyl group.
Fourteen esters (formate, acetate, propionate, butyrate, hexanoate, heptanoate, and benzoate) located at C-11 of 11 beta-hydroxyesterone and 11 beta-hydroxyestradiol-17 beta were synthesized and evaluated for uterotropic and gonadotropin release inhibition in rats, as well as their ability to displace (3H) estradiol-17 beta from the rat uterine cytosolic estrogen receptor. The most potent uterotropic agent was 11 beta-formoxyestrone which was 1,625 or 2,500 times as active as 11 beta-hydroxyesterone in the uterotropic or gonadotropin release inhibition assay, respectively. 11 beta-Formoxyestrone was 7.5 times as uterotropic as estradiol-17 beta and equal to estradiol-17 beta in inhibiting gonadotropin release. However, the most potent inhibitor of gonadotropin release was 11 beta-acetoxy-estradiol-17 beta which had 133% of the activity of estradiol-17 beta, although it had only 38% of the activity of estradiol-17 beta in the uterotropic assay. Esters larger than the acetoxy group showed sharply decreased activities in either assay. Despite the high estrogenic potency of the 11-formates or 11-acetates, they were rather weak (6% to 35% as active as estradiol-17 beta) in displacing (3H) estradiol-17 beta from the rat uterine cytosolic estrogen receptor.
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004952:Esters; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D006062:Gonadotropins / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000378:metabolism
D004952:Esters; D004967:Estrogens; D006062:Gonadotropins; D011960:Receptors, Estrogen; D004958:Estradiol