Elsevier, Bioorganic and Medicinal Chemistry Letters, 19(23), p. 5397-5400, 2013
DOI: 10.1016/j.bmcl.2013.07.047
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In the last decade the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-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 11β-HSD1 inhibitors bearing an arylsulfonylpiperazine scaffold. Optimization of the initial lead resulted in compound 11 that selectively inhibits 11β-HSD1 (IC50=0.7μM).