Discovery of 7-aryl-substituted (1,5-naphthyridin-4-yl)ureas as aurora kinase inhibitors.
ChemMedChem
; 9(1): 217-32, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24273104
ABSTRACT
As part of our research projects to identify new chemical entities of biological interest, we developed a synthetic approach and the biological evaluation of (7-aryl-1,5-naphthyridin-4-yl)ureas as a novel class of Aurora kinase inhibitors for the treatment of malignant diseases based on pathological cell proliferation. 1,5-Naphthyridine derivatives showed excellent inhibitory activities toward Aurora kinases A and B, and the most active compound, 1-cyclopropyl-3-[7-(1-methyl-1H-pyrazol-4-yl)-1,5-naphthyridin-4-yl]urea (49), displayed IC50 values of 13 and 107â
nM against Aurora kinases A and B, respectively. In addition, the selectivity toward a panel of seven cancer-related protein kinases was highlighted. In vitro ADME properties were also determined in order to rationalize the difficulties in correlating antiproliferative activity with Aurora kinase inhibition. Finally, the good safety profile of these compounds imparts promising potential for their further development as anticancer agents.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ureia
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Inibidores de Proteínas Quinases
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Aurora Quinase A
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Aurora Quinase B
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article