3-N-alkyloxyestradiol derivatives were synthesized, characterized and tested for activity in MCF-7 human breast cancer cells. Among the compounds, the diisopropyl and piperidinyl derivatives were found to be more active than 4-hydroxytamoxifen (HO-Tam), the active metabolite of tamoxifen based upon IC(50) values. The IC(50)s were correlated with structures using molecular modeling.