In the last decade the inhibition of the enzyme 11¦Â-hydroxysteroid dehydrogenase 1 (11¦Â-HSD1) emerged as a promising new strategy to treat diabetes and several metabolic syndrome phenotypes. Using a molecular modeling approach and classical bioisosteric studies, we discovered a new class of 11¦Â-HSD1 inhibitors bearing an arylsulfonylpiperazine scaffold. Optimization of the initial lead resulted in compound 11 that selectively inhibits 11¦Â-HSD1 (IC50 = 0.7 ¦ÌM).