11-BETA-AMIDOALKOXYPHENYL ESTRADIOLS, A NEW SERIES OF PURE ANTIESTROGENS

11 beta-Amidoalkoxyphenyl estradiols, a series of new antiestrogens, h ave been prepared and compared with tamoxifen (TAM) and 4-hydroxytamox ifen (OH-TAM). In vitro, these compounds were up to 20 times as active as OH-TAM on estradiol (E2)-stimulated MCF-7 cells. Unlike TAM or OH- TAM which were inactive, they displayed potent growth inhibitory effec ts on MCF-7 cells stimulated by a cocktail of epidermal growth factor and platelet derived growth factor. One of the most active compounds, 5e, was tested in vivo for its antiuterotrophic and antitumoral activi ties: it proved to be fully antiuterotrophic at 3 mg/kg subcutaneously in mice while being devoid of any uterotrophic activity. It inhibited the E2-induced growth of MCF-7 tumors implanted in nude mice and prev ented the partial agonistic activity of TAM on MCF-7 tumor growth in o variectomized mice. Moreover, on MCF-7 variant tumors, 5e, unlike TAM, did not display any proliferative activity, but inhibited the TAM-ind uced growth. Overall, these results show that this new series of compo unds displays an improved activity profile compared with that of TAM, on tests relevant to human breast cancer treatment.