Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases.
Bioorg Med Chem Lett
; 22(14): 4750-5, 2012 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-22695126
ABSTRACT
In an effort to identify kinase inhibitors with dual KDR/Aurora B activity and improved aqueous solubility compared to the Abbott dual inhibitor ABT-348, a series of novel pyrazole pyrimidines structurally related to kinase inhibitor AS703569 were prepared. SAR work provided analogs with significant cellular activity, measureable aqueous solubility and moderate antitumor activity in a mouse tumor model after weekly ip dosing. Unfortunately these compounds were pan-kinase inhibitors that suffered from narrow therapeutic indices which prohibited their use as antitumor agents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Pirimidinas
/
Proteínas Serina-Treonina Quinases
/
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
/
Inibidores de Proteínas Quinases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article