Synthesis of Chimeric 7α-Substituted Estradiol Derivatives Linked to Cholesterol and Cholesterylamine

We report the synthesis of 7α-substituted β-estradiol derivatives bearing side chains terminated with cholesterol and 3β-cholesterylamine. These chimeric compounds were designed to exhibit high affinity for estrogen receptors (ERs) and cellular plasma membranes to potentially enable regulated uptake of ERs by mammalian cells. Evaluation with recombinant yeast reporting compound-mediated ER dimerization revealed potencies similar to the antiestrogen ICI 182780. Compounds that efficiently deliver dominant negative ERs into cells may provide novel therapeutics against breast cancers.