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Merck

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

Bioorganic & medicinal chemistry letters (2006-01-18)
Wanying Sun, Lovji D Cama, Elizabeth T Birzin, Sudha Warrier, Louis Locco, Ralph Mosley, Milton L Hammond, Susan P Rohrer
RESUMEN

A series of 6H-benzo[c]chromen-6-one and 6H-benzo[c]chromene derivatives were prepared, and the affinity and selectivity for ERalpha and ERbeta was measured. Many of the analogs were found to be potent and selective ERbeta 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 ERbeta<10nM potency and >100-fold selectivity over ERalpha.

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