2. Academic Validation
  3. Aglycone exploration of C-arylglucoside inhibitors of renal sodium-dependent glucose transporter SGLT2

Aglycone exploration of C-arylglucoside inhibitors of renal sodium-dependent glucose transporter SGLT2

  • Bioorg Med Chem Lett. 2008 Sep 1;18(17):4770-3. doi: 10.1016/j.bmcl.2008.07.109.
Bruce A Ellsworth 1,  Wei Meng,  Manorama Patel,  Ravindar N Girotra,  Gang Wu,  Philip M Sher,  Deborah L Hagan,  Mary T Obermeier,  William G Humphreys,  James G Robertson,  Aiying Wang,  Songping Han,  Thomas L Waldron,  Nathan N Morgan,  Jean M Whaley,  William N Washburn
Affiliations

Affiliation

  • 1 Research and Development, Bristol Myers Squibb Co., PO Box 5400, Princeton, NJ 08543-5400, USA.
PMID: 18707880 DOI: 10.1016/j.bmcl.2008.07.109
Abstract

Inhibition of sodium-dependent glucose transporter 2 (SGLT2), the transporter that is responsible for renal re-uptake of glucose, leads to glucosuria in Animals. SGLT-mediated glucosuria provides a mechanism to shed excess plasma glucose to ameliorate diabetes-related hyperglycemia and associated complications. The current study demonstrates that the proper relationship of a 4'-substituted benzyl group to a beta-1C-phenylglucoside is important for potent and selective SGLT2 inhibition. The lead C-arylglucoside (7a) demonstrates superior metabolic stability to its O-arylglucoside counterpart (4) and it promotes glucosuria when administered in vivo.

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