Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy

Stephen A. Thomson,Pierette Banker,D. Mark Bickett,Joyce A. Boucheron,H. Luke Carter,Daphne C. Clancy,Joel P. Cooper,Scott H. Dickerson,Dulce M. Garrido,Robert T. Nolte,Andrew J. Peat,Lauren R. Sheckler,Steven M. Sparks,Francis X. Tavares,Liping Wang,Tony Y. Wang,James E. Weiel

Bioorganic & Medicinal Chemistry Letters（2009）

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摘要

Use of an X-ray crystal structure allowed for the optimization of the anthranilimide-based glycogen phosphorylase inhibitors to give compound 23 which displayed both in vitro potency versus GPa and in vivo efficacy in a mouse model of type 2 diabetes.

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关键词

Glycogen,Phosphorylase,Inhibitor,Anthranilimide,Glucagon,Challenge,Antidiabetic

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