Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1363355 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
Glucokinase activators (GKAs) are currently under investigation as potential antidiabetic agents by many pharmaceutical companies. Most of GKAs reported previously possess N-aminothiazol-2-yl amide moiety in their structures because the aminothiazole moiety interacts with glucokinase (GK) and shows strong GK activation. During the development of N-aminothiazol-2-yl amide derivatives, we identified a bioactivation and metabolic liability of 2-aminothizole substructure of GKA 3 by assessing covalent binding, metabolites in liver microsomes and glutathione (GSH) trap assay.
Graphical abstractThe in vitro covalent binding results that were observed during the course of evaluating the compound 3 for the treatment of type-2 diabetes are described.Figure optionsDownload full-size imageDownload as PowerPoint slide