Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1,2,3-benzotriazole lead.
Bioorg Med Chem Lett
; 23(5): 1486-92, 2013 Mar 01.
Article
de En
| MEDLINE
| ID: mdl-23352510
ABSTRACT
A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, respectively), with bioavailability in rats and suitable for further in vivo pharmacological evaluation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pyrimidines
/
Triazoles
/
JNK Mitogen-Activated Protein Kinases
/
Inhibiteurs de protéines kinases
Limites:
Animals
/
Humans
Langue:
En
Journal:
Bioorg Med Chem Lett
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2013
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique