Discovery of 4-heteroarylbicyclo[2.2.2]octyltriazoles as potent and selective inhibitors of 11β-HSD1: Novel therapeutic agents for the treatment of metabolic syndrome

Replacement of the pentyl chain on our original bicyclo[2.2.2]octyltriazole leads 1 and 2 has led to the discovery that heteroaryl substituted bicyclo[2.2.2]octyltriazoles are potent and selective 11β-hydroxysteroid dehydrogenase type I (11β-HSD1) inhibitors with excellent pharmacokinetic profiles.

Graphical abstractHeteroaryl substituted bicyclo[2.2.2]octyltriazoles have been shown to be potent and selective inhibitors of 11β-hydroxysteroid dehydrogenase type I (11β-HSD1) with excellent pharmacokinetic profiles. Compound 11 is a 2.2 nM inhibitor of human 11β-HSD1 enzyme.Figure optionsDownload full-size imageDownload as PowerPoint slide