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

Autor:	David M. Bickett, Pierette Banker, Daphne C. Clancy, Joyce A. Boucheron, Stephen A. Thomson, James E. Weiel, and Andrew J. Peat, Dulce Garrido, Steven M. Sparks, Francis X. Tavares, Lauren R. Sheckler, Joel P. Cooper, Scott Howard Dickerson, Liping Wang, Tony Y. Wang, Robert T. Nolte, H.L. Carter
Rok vydání:	2008
Předmět:	Blood Glucose Clinical Biochemistry Molecular Conformation Pharmaceutical Science Crystallography X-Ray Biochemistry Glucagon Glycogen phosphorylase chemistry.chemical_compound Mice Structure-Activity Relationship In vivo Drug Discovery Transferase Potency Structure–activity relationship Animals Combinatorial Chemistry Techniques Hypoglycemic Agents Urea ortho-Aminobenzoates Molecular Biology Glycogen Molecular Structure Chemistry Organic Chemistry Glycogen Phosphorylase Crystallography Disease Models Animal Diabetes Mellitus Type 2 Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 19(4)
ISSN:	1464-3405
Popis:	Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::315bf00dccdab187675054ab81ac0fef https://pubmed.ncbi.nlm.nih.gov/19138846 Zobrazit plný text záznamu Full Text from ScienceDirect