Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372812 | Bioorganic & Medicinal Chemistry Letters | 2008 | 4 Pages |
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 β-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.
Graphical abstractThe evolution of potent and selective C-arylglucoside SGLT2 inhibitors from lead 6 to 7a is described.Figure optionsDownload full-size imageDownload as PowerPoint slide