Structure-Based Design of Estrogen Receptor-β Selective Ligands

We present the structure-based optimization of a series of estrogen receptor-β (ERβ) selective ligands. X-ray cocrystal structures of these ligands complexed to both ERα and ERβ are described. We also discuss how molecular modeling was used to take advantage of subtle differences between the two binding cavities in order to optimize selectivity for ERβ over ERα. Quantum chemical calculations are utilized to gain insight into the mechanism of...