Design and Synthesis of Estrogen Receptor Coactivator Binding Inhibitors

Abstract

Key hydrophobic and hydrogen bonding moieties were incorporated onto a variety of core scaffolds including amphipathic benzene, bicyclo[2.2.2]octane, and urea, resulting in three different series of compounds that could be utilized as coactivator binding inhibitors (CBIs). A fluorescence-based assay was used to evaluate the ability of the CBIs to effectively block the ER-coactivator interaction. The most effective compounds synthesized were amphipathic benzene derivatives with Ki's of 7 and 4 muM, which are the best in vitro affinities to date in our research group.