6H-Benzo[c]chromen-6-one derivatives as selective ERβ agonists

A series of 6H-benzo[c]chromen-6-one and 6H-benzo[c]chromene derivatives were prepared, and the affinity and selectivity for ERα and ERβ was measured. Many of the analogs were found to be potent and selective ERβ agonists. Bis hydroxyl at positions 3 and 8 is essential for activity in a HTRF coactivator recruitment assay. Additional modifications at both phenyl rings led to compounds with ERβ < 10 nM potency and >100-fold selectivity over ERα.

Graphical abstractA series of 6H-benzo[c]chromen-6-one and 6H-benzo[c]chromene derivatives were prepared. Many of the analogs were found to be potent and selective ERβ agonists. Bis hydroxyl at positions 3 and 8 are essential for activity in a HTRF coactivator recruitment assay. Additional modifications at both phenyl rings led to compounds with ERβ <10 nM potency and >100-fold selectivity over ERα.Figure optionsDownload full-size imageDownload as PowerPoint slide