SYNTHESIS OF SUBSTITUTED 2-β-D-GLYCOPYRANOSYL BENZIMIDAZOLES FOR INHIBITION OF GLYCOGEN PHOSPHORYLASE

摘要

Inhibitors of glycogene phosphorylase (GP) can be considered as possible means for intervention in type 2 diabetes, cardiovascular disease, and tumor growth. A large array of compounds were shown to have inhibitory effect against this enzyme. Among glucose based inhibitors C-glucosyl heterocycles exhibit inhibition of GP in the low micromolar range, and 2-β-D-glucopyranosyl benzimidazole (1, R = H) was one of the first compounds4 to show this property. X-Ray crystallographic investigation of 1 (R = H) in complex with rabbit muscle GP revealed that besides the catalytic site the compound bound also to the so called new allosteric site, and a new binding cleft called the imidazole site was also discovered.