Piperazine Sulfonamides as Potent, Selective, and Orally Available 11beta-Hydroxysteroid Dehydrogena
June 27th, 2008 | by admin |Piperazine Sulfonamides as Potent, Selective, and Orally Available 11beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitors with Efficacy in the Rat Cortisone-Induced Hyperinsulinemia Model.
11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is the enzyme that converts cortisone to cortisol. Evidence suggests that selective inhibition of 11beta-HSD1 could treat diabetes and metabolic syndrome. Presented herein are the synthesis, structure-activity relationship, and in vivo evaluation of piperazine sulfonamides as 11beta-HSD1 inhibitors. Through modification of our initial lead 5a, we have identified potent and selective 11beta-HSD1 inhibitors such as 13q and 13u with good pharmacokinetic properties.
Xiang J, Wan ZK, Li HQ, Ipek M, Binnun E, Nunez J, Chen L, McKew JC, Mansour TS, Xu X, Suri V, Tam M, Xing Y, Li X, Hahm S, Tobin J, Saiah E.
jxiang@wyeth.com.