The nonsteroidal antiestrogen drug tamoxifen is the endocrine treatment of choice for estrogen receptor positive breast cancer, while the related estrogen receptor antagonist raloxifene is an effective therapeutic intervention for osteoporosis. We report the development of a series of hydroxylated 2-benzyl-1,1-diarylbut-2-enes containing a flexible core scaffold structure differing from the 1,1,2-triarylethylene typical of tamoxifen analogues. In this novel structure, a benzylic methylene group acts as a flexible hinge linking the aryl ring C and the ethylene group. The target products were synthesized using a McMurry coupling (titanium tetrachloride/zinc mediated) procedure. In this study, introduction of hydroxyl, ether and ester substitution on ring C was explored in an attempt to correlate possible metabolic activation in Ring C with antiproliferative activity. These Ring C substituted products showed potent antiproliferative activity against the MCF-7 human breast cancer cell line. The compounds were also shown to have high binding affinity for the estrogen receptor (IC(50) values in the low nanomolar range) together with up to 17 fold selectivity for ERalpha/beta. Some compounds demonstrated antiestrogenic activity in the Ishikawa cells at 40 nM without estrogenic stimulation. The products also displayed a pro-apoptotic effect in MCF-7 cells in a flow cytometry based assay. In a computational study, docked structures of the active compounds were compared with the X-ray crystal structures for the complexes of ERalpha with 4-hydroxytamoxifen and ERbeta with raloxifene. The novel ligands are predicted to bind to the ERalpha and ERbeta in an antiestrogenic orientation, with expected differences obtained in the alignment of the benzylic ring C within the ligand binding domain.