Discovery of Pyridones As Oral AMPK Direct Activators.
ACS Med Chem Lett
; 4(7): 632-6, 2013 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-24900722
ABSTRACT
AMP-activated protein kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme that is activated in shortage of energy and suppressed in its surfeit. AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity, alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory changes. Thus, AMPK is a well-received therapeutic target for type 2 diabetes and other metabolic disorders. Here, we will report the discovery of pyrrolopyridone derivatives as AMPK direct activators. We will illustrate the synthesis and structure-activity relationships of the series as well as some pharmacokinetic results. Some compounds exhibited encouraging oral exposure and were evaluated in a mouse diabetic model. Compound 17 showed oral activity at 30 mg/kg on blood glucose.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França