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ID: ALA3797116

Journal: Bioorg Med Chem Lett

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

Authors: Cao X, Zhang W, Yan X, Huang Z, Zhang Z, Wang P, Shen J.

Abstract: 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.

CiteXplore: 27025345

DOI: 10.1016/j.bmcl.2016.03.065