Steroidal pure antioestrogens.
The effects of some novel 7 alpha-alkyl amide analogues of oestradiol on the rat and mouse uterus have been measured. The compound ICI 164,384 [N-n-butyl-N-methyl-11-(3,17 beta-dihydroxyoestra-1,3,5(10)-trien-7 alpha-yl) undecamide] was entirely devoid of oestrogenic activity in the rat and mouse uterus but completely blocked the uterine stimulatory effects of oestradiol and of tamoxifen. Biological activity was confined to 7 alpha-isomers. The affinity of ICI 164,384 for the rat uterus oestrogen receptor (0.19) was substantially greater than that of tamoxifen (0.025 c.f. oestradiol = 1). The compound inhibited oestradiol-induced growth of ZR-71-1 cells in a dose-dependent manner in vitro. ICI 164,384 thus has the characteristics of a pure antagonist of oestrogen action.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D051379:Mice; D053284:Polyunsaturated Alkamides; D051381:Rats; D013629:Tamoxifen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; D004958:Estradiol; C051781:ICI 164384