Structural derivatives of tamoxifen and oestradiol 3-methyl ether as potential alkylating antioestrogens

The oestrogenic and antioestrogenic activity of potential alkylating derivatives of tamoxifen and oestradiol 3-methyl ether have been compared with tamoxifen and oestradiol benzoate in the immature rat. Although all the tamoxifen derivatives demonstrated an ability to inhibit the binding of [³H]oestradiol to rabbit or rat uterine oestrogen receptors in vitro, none of the compounds was as potent as tamoxifen in tests for antioestrogenic activity in vivo. The potential alkylating derivatives of oestradiol 3-methyl ether were not antioestrogenic. The properties of all the compounds in vivo did not suggest irreversible effects upon the uterus. Since the assays in vitro did not predict activity in vivo the results indicate that only agents with very high affinity for the oestrogen receptor that do not potentially require metabolic activation may be useful in vivo.