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

作者：Evans Karen A^*; Li Yue H; Coppo Frank T; Graybill Todd L; Cichy Knight Maria; Patel Mehul; Gale Jennifer; Li Hu; Thrall Sara H; Tew David; Tavares Francis; Thomson Stephen A; Weiel James E; Boucheron Joyce A; Clancy Daphne C; Epperly Andrea H; Golden Pamela L

来源：Bioorganic & Medicinal Chemistry Letters, 2008, 18(14): 4068-4071.

DOI：10.1016/j.bmcl.2008.05.102

• human liver glycogen phosphorylase
• glycogen phosphorylase inhibitors
• solid-phase synthesis

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 (IC(50) = 80 nM). The SAR scope, synthetic strategy, and in vitro results for this series are presented herein.

• 出版日期2008-7-15