Abstract—Aseries of novel benzamide derivatives was designed, synthesized, and their inhibitory activities against glycogen phosphorylase
(GP) in the direction of glycogen synthesis by the release of phosphate from glucose-1-phosphate were evaluated. The structureactivity
relationships (SAR) of these compounds are also presented. Within this series of compounds, 4m is the most potent GPa
inhibitor (IC50 = 2.68 lM), which is nearly 100 times more potent than the initial compound 1. Analysis of mapping between
pharmacophores of different binding sites and each compound demonstrated that these benzamide derivatives bind at the dimer
interface of the rabbit muscle enzyme, and possible docking modes of compound 4m were explored by molecular docking simulation.