6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists.
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.
Sun
Wanying
W
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. wanying_sun@merck.com
Cama
Lovji D
LD
Birzin
Elizabeth T
ET
Warrier
Sudha
S
Locco
Louis
L
Mosley
Ralph
R
Hammond
Milton L
ML
Rohrer
Susan P
SP
D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000378:metabolism; D015200:Fluoroimmunoassay; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D001555:Benzene Derivatives; D001578:Benzopyrans; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands