5-amino-pyrazoles as potent and selective p38α inhibitors.
Bioorg Med Chem Lett
; 20(23): 6886-9, 2010 Dec 01.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrazoles
/
Mitogen-Activated Protein Kinase 14
/
Protein Kinase Inhibitors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2010
Document type:
Article
Affiliation country:
United States