Document Report Card

ID: ALA1135754

Journal: J Med Chem

Title: Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and selective inhibitors of the 11beta-hydroxysteroid dehydrogenase type 1.

Authors: Barf T, Vallgårda J, Emond R, Häggström C, Kurz G, Nygren A, Larwood V, Mosialou E, Axelsson K, Olsson R, Engblom L, Edling N, Rönquist-Nii Y, Ohman B, Alberts P, Abrahmsén L.

Abstract: Novel antidiabetic arylsulfonamidothiazoles are presented that exert action through selective inhibition of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme, thereby attenuating hepatic gluconeogenesis. The diethylamide derivative 2a was shown to potently inhibit human 11beta-HSD1 (IC(50) = 52 nM), whereas the N-methylpiperazinamide analogue 2b only inhibited murine 11beta-HSD1 (IC(50) = 96 nM). Both compounds showed >200-fold selectivity over human and murine 11beta-HSD2. 2b was subsequently shown to reduce glucose levels in diabetic KKA(y) mice, substantiating the 11beta-HSD1 enzyme as a target for the treatment of type 2 diabetes.

CiteXplore: 12190302

DOI: 10.1021/jm025530f