Identification of novel series of pyrazole and indole-urea based DFG-out PYK2 inhibitors.
Bioorg Med Chem Lett
; 22(24): 7523-9, 2012 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-23153798
ABSTRACT
Previous drug discovery efforts identified classical PYK2 kinase inhibitors such as 2 and 3 that possess selectivity for PYK2 over its intra-family isoform FAK. Efforts to identify more kinome-selective chemical matter that stabilize a DFG-out conformation of the enzyme are described herein. Two sub-series of PYK2 inhibitors, an indole carboxamide-urea and a pyrazole-urea have been identified and found to have different binding interactions with the hinge region of PYK2. These leads proved to be more selective than the original classical inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Ureia
/
Inibidores de Proteínas Quinases
/
Quinase 2 de Adesão Focal
/
Indóis
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos