Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors.
Bioorg Med Chem Lett
; 22(12): 4089-93, 2012 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-22595176
ABSTRACT
Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of a structurally diverse series of carbon-linked quinoline triazolopyridinones, which demonstrates nanomolar inhibition of c-Met kinase activity. This novel series of inhibitors exhibits favorable pharmacokinetics as well as potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridonas
/
Quinolinas
/
Triazoles
/
Proteínas Proto-Oncogénicas c-met
/
Inhibidores de Proteínas Quinasas
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos