5-amino-pyrazoles as potent and selective p38α inhibitors.
Bioorg Med Chem Lett
; 20(23): 6886-9, 2010 Dec 01.
Article
de 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pyrazoles
/
Mitogen-Activated Protein Kinase 14
/
Inhibiteurs de protéines kinases
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Bioorg Med Chem Lett
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2010
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique