1.
Bioorg Med Chem Lett
; 20(17): 5133-8, 2010 Sep 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-20673630
RESUMO
Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described.
Assuntos
Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/efeitos dos fármacos , Triazóis/química , Triazóis/farmacologia , Quinase 1 do Ponto de Checagem , Cristalografia por Raios X , Descoberta de Drogas , Modelos Moleculares , Relação Estrutura-Atividade
2.
Bioorg Med Chem Lett
; 19(3): 1026-9, 2009 Feb 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-19097792
RESUMO
A series of amidoheteroaryl compounds were designed and synthesized as inhibitors of B-Raf kinase. Several compounds from the series show excellent potency in biochemical, phenotypic and mode of action cellular assays. Potent examples from the series have also demonstrated good plasma exposure following an oral dose in rodents and activity against the Ras-Raf pathway in tumor bearing mice.