【文章名】Piperazine Sulfonamides as Potent, Selective, and Orally Available 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitors with Efficacy in the Rat Cortisone-Induced Hyperinsulinemia Model.
Piperazine Sulfonamides as Potent, Selective, and Orally Available 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitors with Efficacy in the Rat Cortisone-Induced Hyperinsulinemia Model.
[摘要]：11b-Hydroxysteroid dehydrogenase type 1 (11b-HSD1) is the enzyme that converts cortisone to cortisol. Evidence suggests that selective inhibition of 11b-HSD1 could treat diabetes and metabolic syndrome. Presented herein are the synthesis, structure-activity relationship, and in vivo evaluation of piperazine sulfonamides as 11b-HSD1 inhibitors. Through modification of our initial lead I (R1 = 3,4-Cl2, R2 = H, X = N), we have identified potent and selective 11b-HSD1 inhibitors such as I [R1 = 3-(1,2,4-triazol-1-yl), 3-(MeO2CCMe2O), R2 = F, X = C] with good pharmacokinetic properties.
