Discovery and structure-activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2.
Bioorg Med Chem Lett
; 22(13): 4358-61, 2012 Jul 01.
Article
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| MEDLINE
| ID: mdl-22633690
ABSTRACT
We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pirazinas
/
Quinasa de la Caseína II
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Inhibidores de Proteínas Quinasas
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Indazoles
Idioma:
En
Revista:
Bioorg Med Chem Lett
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón