Phenylcyclobutyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type I

3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure–activity relationships are presented.