Discovery of Novel N-β-d-Xylosylindole Derivatives as Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for the Management of Hyperglycemia in Diabetes
2011
A novel series of N-linked β-d-xylosides were synthesized and evaluated for inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) in a cell-based assay. Of these, the 4-chloro-3-(4-cyclopropylbenzyl)-1-(β-d-xylopyranosyl)-1H-indole 19m was found to be the most potent inhibitor, with an EC50 value similar to that of the natural SGLT2 inhibitor phlorizin. Further studies in Sprague−Dawley (SD) rats indicated that 19m significantly increased urine glucose excretion in a dose-dependent manner with oral administration. The antihyperglycemic effect of 19m was also observed in streptozotocin (STZ) induced diabetic SD rats. These results described here are a good starting point for further investigations into N-glycoside SGLT2 inhibitors.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
24
References
37
Citations
NaN
KQI