Amino acid anthranilamide derivatives as a new class of glycogen phosphorylase inhibitors

A series of amino acid anthranilamide derivatives identified from a high-throughput screening campaign as novel, potent, and glucose-sensitive inhibitors of human liver glycogen phosphorylase a are described. A solid-phase synthesis using Wang resin was also developed which provided efficient access to a variety of analogues, and resulted in the identification of key structure–activity relationships, and the discovery of a potent exemplar (IC50 = 80 nM). The SAR scope, synthetic strategy, and in vitro results for this series are presented herein.