5-amino-pyrazoles as potent and selective p38α inhibitors.
Bioorg Med Chem Lett
; 20(23): 6886-9, 2010 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-21035336
ABSTRACT
The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production. Compound 2j was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38α is also disclosed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Proteína Quinase 14 Ativada por Mitógeno
/
Inibidores de Proteínas Quinases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos