Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes

  • J Med Chem. 2008 Mar 13;51(5):1145-9. doi: 10.1021/jm701272q.
Wei Meng  1 ,  Bruce A Ellsworth ,  Alexandra A Nirschl ,  Peggy J McCann ,  Manorama Patel ,  Ravindar N Girotra ,  Gang Wu ,  Philip M Sher ,  Eamonn P Morrison ,  Scott A Biller ,  Robert Zahler ,  Prashant P Deshpande ,  Annie Pullockaran ,  Deborah L Hagan ,  Nathan Morgan ,  Joseph R Taylor ,  Mary T Obermeier ,  William G Humphreys ,  Ashish Khanna ,  Lorell Discenza ,  James G Robertson ,  Aiying Wang ,  Songping Han ,  John R Wetterau ,  Evan B Janovitz ,  Oliver P Flint ,  Jean M Whaley ,  William N Washburn
Affiliations
  • 1. Drug Safety Evaluation and Development, Bristol -Myers Squibb Company, Princeton, New Jersey 08543, USA. [email protected]
PMID: 18260618 DOI: 10.1021/jm701272q
Abstract

The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.