3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

Marion Donnier-Marechal (1) , David Goyard (1) , Vincent Folliard , Tibor Docsa (2) , Pál Gergely (2) , Jean-Pierre Praly (1) , Sébastien Vidal (1)

1 CO2GLYCO - Chimie Organique 2-Glycochimie
2 Department of Medicinal Chemistry

Glycogen phosporylase (GP) is a promising target for the control of glycaemia. The design of inhibitors binding at the catalytic site has been accomplished through various families of glucose-based derivatives such as oxadiazoles. Further elaboration of the oxadiazole aromatic aglycon moiety is now reported with 3-glucosyl-5-amino-1,2,4-oxadiazoles synthesized by condensation of a C-glucosyl amidoxime with N,N’-dialkylcarbodiimides or Vilsmeier salts. The 5-amino group introduced on the oxadiazole scaffold was expected to provide better inhibition of GP through potential additional interactions with the enzyme’s catalytic site; however, no inhibition was observed at 625 µM.

Keywords: oxadiazole, Vilsmeier salt, amidoxime, carbodiimide, glycogen phosphorylase

Domains: Organic chemistry

Marion Donnier-Marechal, David Goyard, Vincent Folliard, Tibor Docsa, Pál Gergely, et al.. 3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors. Beilstein Journal of Organic Chemistry, 2015, 11, pp.499-503. ⟨10.3762/bjoc.11.56⟩. ⟨hal-02123939⟩