Potent Estrogen Receptor Ligands Based on Bisphenols with a Globular Hydrophobic Core

Candidate estrogen receptor (ER) ligands with two phenolic residues on a three-dimensional hydrophobic core structure (carborane, bicyclo[2.2.2]octene, or adamantane) were synthesized and biologically evaluated. The biological properties of the ligands were markedly dependent on the nature of the hydrophobic core structure. Bis(4-hydroxyphenyl)-o-carborane (<BO>6</BO>) was a partial agonist/antagonist for ER. 1,2-Bis(4-hydroxyphenyl)bicyclo[2.2.2]octene (<BO>10</BO>) exhibited potent agonist activity for ER, even though the two phenolic groups are located similarly to those of <BO>6</BO>.