Design, synthesis, and biological evaluation of cyclopropyl analogues of stilbene with raloxifene side chain as subtypeselective ligands for estrogen receptor

We have designed the cyclopropane analog ofstilbene as subtype-selective ligands for estrogen receptorbased on the bioisosterism that cyclopropane could act asalkene bioisoster. Three cyclopropane analogs were preparedefficiently starting from 4-benzyloxybenzaldehyde,and evaluated for their binding to estrogen receptors ERaand ERb. These cyclopropane analogs were also found tobe full agonists in estrogen receptor-mediated gene transcriptionassay. Compared to the stilbene analogs such astamoxifen and raloxifene, the three cyclopropane analogsshowed lower binding affinity for estrogen receptor, buthigher subtype selectivity for ERa. The structure–activityrelationship revealed from this study might provide cluesfor improving subtype selectivity for ERa. KCI Citation Count: 8