Modification on the O-glucoside of Sergliflozin-A: A new strategy for SGLT2 inhibitor design.

Poor pharmacokinetic stability is one of the issues of O -glucoside SGLT2 inhibitors in clinical trials, hence C -glucoside inhibitors have been developed and extensively applied. Herein, we provided an alternative approach to improve the pharmacokinetic stability of such inhibitors. Nine derivatives of Sergliflozin-A with modifications on the O -glucoside fragment were prepared, among which the 4- O -methyl derivative exhibited similar pharmacodynamics potency in excreted glucose urine test. Most attractively, significantly increased pharmacokinetic stability was observed for 4- O -methyl derivative of O -glucosides. This work proved that modification on the O -glucoside fragment could be a promising approach to the future SGLT2 inhibitor design. [ABSTRACT FROM AUTHOR]