Design and synthesis of novel estrogen receptor antagonists with acetal containing biphenylmethane skeleton

Abstract

Novel compounds bearing acetal groups in their biphenylmethane skeletons were synthesized in moderate yields from benzophenone derivative. Compound 1 did not exhibit antagonistic activity against the ERα estrogen receptor; however, compounds 2, 3, and 4 exhibited potent ERα antagonistic activities. A small difference in the ERα antagonistic activities of the stereoisomers was observed. It was suggested that the methyl groups on the acetal moieties were responsible for the observed ERα antagonistic activities of the compounds. These results could be attributed to interactions of the methyl groups of the acetal functional groups with the hydrophobic binding residues of the binding site.