2. Academic Validation
  3. Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and selective inhibitors of the 11beta-hydroxysteroid dehydrogenase type 1

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

  • J Med Chem. 2002 Aug 29;45(18):3813-5. doi: 10.1021/jm025530f.
Tjeerd Barf 1,  Jerk Vallgårda,  Rikard Emond,  Charlotta Häggström,  Guido Kurz,  Alf Nygren,  Vivienne Larwood,  Erifili Mosialou,  Kent Axelsson,  Rolf Olsson,  Lars Engblom,  Naimie Edling,  Yuko Rönquist-Nii,  Birgitta Ohman,  Peteris Alberts,  Lars Abrahmsén
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Biovitrum, Box 6443, SE-751 37, Uppsala, Sweden. tjeerd.barf@biovitrum.com
PMID: 12190302 DOI: 10.1021/jm025530f
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.

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