A series of benzamide derivatives which can simultaneously inhibit glycogen phosphorylase (GP) and
activate glucokinase (GK) were prepared and evaluated. The structure–activity relationships (SAR) of
these compounds were also presented. Among these, compounds 12, 13l, 13q, and 13v showed moderate
activities towards both GK and GP. Compound 13h inhibited hLGP with an IC50 of 8.95 lM and activated
GK with an EC50 of 1.87 lM. The possible binding modes of compounds 12, 13l, 13h, and 13q with GP and
GK were also explored by molecular docking simulation.