Novel antioestrogens without partial agonist activity

Abstract

The oestrogenic and antioestrogenic properties of some novel 7 alpha-alkyl amide derivatives of 17 beta-oestradiol have been measured in rats and mice. The compound ICI 164384 was devoid of oestrogenic activity in the uterus and vagina of both species and on the hypothalamic-pituitary axis of the rat. ICI 164384 blocked completely the uterotrophic action of exogenous and endogenous oestradiol and of the partial agonist antioestrogens typified by tamoxifen. Unlike tamoxifen ICI 164384 did not promote premature vaginal opening in neonatal rats. The affinity of ICI 164384 for the rat uterus oestrogen receptor was substantially greater than that of tamoxifen. In MCF-7 and ZR-75-1 breast cancer cells in tissue culture ICI 164384 was a more potent inhibitor of cell growth than tamoxifen and growth inhibition was reversed by oestradiol. The properties of ICI 164384 satisfy many of the criteria which define pure antioestrogens.