Piperazine sulfonamides as potent, selective, and orally available 11β-hydroxysteroid dehydrogenase type 1 inhibitors with efficacy in the rat cortisone-induced hyperinsulinemia model

Article abstract of DOI:10.1021/jm8004948

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is the enzyme that converts cortisone to cortisol. Evidence suggests that selective inhibition of 11β-HSD1 could treat diabetes and metabolic syndrome. Presented herein are the synthesis, structure-activity relationship, and in vivo evaluation of piperazine sulfonamides as 11β-HSD1 inhibitors. Through modification of our initial lead 5a, we have identified potent and selective 11β-HSD1 inhibitors such as 13q and 13u with good pharmacokinetic properties.