Naturally occurring pentacyclic triterpenes (PT), a novel class of inhibitors against glycogen phosphorylase
(GP), hold promise for the treatment of type-2 diabetes and other diseases with disorders in
glycogen metabolism. To identify novel and more potent GP inhibitors, the receptor-based comparative
molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) approaches
were performed to investigate the quantitative structureeactivity relationships (QSAR) among 106 PT
analogues. The validated models demonstrated that the elongated or bulky substitutions in C17 position
and/or C2, C3 positions are favorable. Then based on the structural information extracted from these
models, 56 derivatives were synthesized and biochemically tested in this study. The IC50 value of the
most potent compound P50 was found to be 1.1 mM.