Androstene-3,5-dienes as ER-β selective SERMs

A series of androstene-3,5-diene derivatives were prepared. Despite lacking the C-3 hydroxyl previously believed necessary for ER activity, some of the analogs retained surprising affinity for ER-β. For example, diene 4 retained excellent selectivity and potency as an ER-β agonist and was more selective for ER-β over the androgen receptor (AR).

Graphical abstractA series of androstene-3,5-dienes (e.g., 4 and 13) is reported. Compound 4 exhibits excellent binding affinity and selectivity for ER-β over ER-α and AR and is a potent ER-β agonist despite lacking the traditional hydroxyl substitution at C-3.Figure optionsDownload full-size imageDownload as PowerPoint slide