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

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 (CH2SO2, CH2S, CH2O, 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.

The synthesis and biological evaluation of a series of potent and selective pyridine amide 11β-HSD1 inhibitors is reported.Figure optionsDownload as PowerPoint slide