Modified 3-alkyl-1,8-dibenzylxanthines as GTP-competitive inhibitors of phosphoenolpyruvate carboxykinase
| Autor: | Pete William Dunten, Mary-Lou Gubler, Gwendolyn Ramsey, Louise H. Foley, Ping Wang, Stanley Wertheimer |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Carboxy-lyases
GTP' Clinical Biochemistry Pharmaceutical Science Biochemistry chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Structure–activity relationship Glucose homeostasis Homeostasis Humans Enzyme Inhibitors Molecular Biology chemistry.chemical_classification biology Organic Chemistry Xanthine Enzyme Glucose chemistry Diabetes Mellitus Type 2 Enzyme inhibitor biology.protein Molecular Medicine Phosphoenolpyruvate Carboxykinase (GTP) Guanosine Triphosphate Phosphoenolpyruvate carboxykinase |
| Zdroj: | Bioorganicmedicinal chemistry letters. 13(20) |
| ISSN: | 0960-894X |
| Popis: | The first non-substrate like inhibitors of human cytosolic phosphoenolpyruvate carboxykinase (PEPCK) competitive with GTP are reported. An effort to discover orally active compounds that improve glucose homeostasis in Type 2 diabetics by reversibly inhibiting PEPCK led to the discovery of 1-allyl-3-butyl-8-methylxanthine (5). We now report modifications at N-1 and C-8 that improved the in vitro activity of the initial xanthine HTS hit by 100-fold and a developing SAR for this class of inhibitor. |
| Databáze: | OpenAIRE |
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