Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity.
Bioorg Med Chem Lett
; 18(6): 1904-9, 2008 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-18294849
ABSTRACT
A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Quinazolinas
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Proteínas Serina-Treonina Quinases
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Neoplasias do Colo
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Inibidores de Proteínas Quinases
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article