Design, synthesis and SAR of novel glucokinase activators

Autor:	Stephen L. Gwaltney, Mark Sabat, Yiqin Wu, Zacharia Cheruvallath, Bumsup Lee, Prasuna Guntupalli, David J. Hosfield, Andrew John Jennings, Jun Feng, Mingnam Tang, Joanne Miura, Haixia Wang
Rok vydání:	2013
Předmět:	Models Molecular Pyridones Clinical Biochemistry Cell Enzyme Activators Mice Obese Pharmaceutical Science Crystallography X-Ray Biochemistry Diabetes Mellitus Experimental Mice Structure-Activity Relationship Glucokinase Drug Discovery Glucokinase activator medicine Animals Hypoglycemic Agents Structure–activity relationship Molecular Biology chemistry.chemical_classification Molecular Structure Organic Chemistry Glucose Tolerance Test Enzyme Activation Mice Inbred C57BL Disease Models Animal Enzyme medicine.anatomical_structure chemistry Design synthesis Drug Design Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 23:2166-2171
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2013.01.093
Popis:	Guided by co-crystal structures of compounds 15, 22 and 30, an SBDD approach led to the discovery of the 6-methyl pyridone series as a novel class of GKAs that potently activate GK in enzyme and cell assays. Anti-diabetic OGTT efficacy was demonstrated with 54 in a mouse model of type 2 diabetes.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c80f2c14ec87914050c121438173989f https://doi.org/10.1016/j.bmcl.2013.01.093 Zobrazit plný text záznamu Full Text from ScienceDirect