Synthesis of C-β-d-glucopyranosyl derivatives of some fused azoles for the inhibition of glycogen phosphorylase

Abstract Annulated C -β- d -glucopyranosyl heterocycles were synthesized and tested as inhibitors of glycogen phosphorylase. 2-(β- d -Glucopyranosyl)-1 H -imidazo[4,5- b ]pyridine was formed by ring-closure of O -perbenzoylated C -β- d -glucopyranosyl formic acid with 2,3-diaminopyridine in the presence of triphenylphosphite. Cyclisations of bromomethyl 2,3,4,6-tetra- O -benzoyl-β- d -glucopyranosyl ketone with a set of 2-aminoheterocycles resulted in constitutionally reversed C -β- d -glucopyranosyl imidazoles fused by pyridine, pyrimidine, thiazole, 1,3,4-thiadiazole, benzothiazole and benzimidazole. O -Debenzoylation of the above compounds was effected by standard transesterification to get the test compounds. The 1 H -imidazo[4,5- b ]pyridine proved to be a low micromolar inhibitor (K i  = 21.1 μM) of rabbit muscle glycogen phosphorylase b, while the other heterocycles displayed weak or no inhibition against the same enzyme.