Pyridine amides as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1

Abstract Several series of pyridine amides were identified as selective and potent 11β-HSD1 inhibitors. The most potent inhibitors feature 2,6- or 3,5-disubstitution on the pyridine core. Various linkers (CH 2 SO 2 , CH 2 S, CH 2 O, S, O, N, bond) between the distal aryl and central pyridyl groups are tolerated, and lipophilic amide groups are generally favored. On the distal aryl group, a number of substitutions are well tolerated. A crystal structure was obtained for a complex between 11β-HSD1 and the most potent inhibitor in this series.