Design, synthesis and biological evaluation of novel acrylamide analogues as inhibitors of BCR-ABL kinase.
Bioorg Med Chem Lett
; 22(16): 5279-82, 2012 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-22789429
ABSTRACT
A series of acrylamide analogues were designed and synthesized from Imatinib and Nilotinib as novel BCR-ABL inhibitors by application of the principle of nonclassical electronic isostere. All new compounds were evaluated for their inhibitory effects on the activity of BCR-ABL kinase and the proliferation of K562 leukemia cancer cells in vitro. The acrylamide analogues in which the substituent in C ring was trifluoromethyl group were identified as highly potent BCR-ABL kinase inhibitors. Compound 13f exhibited an IC(50) value as low as 20.6 nM in ABL kinase inhibition and an IC(50) value of 32.3 nM for antiproliferative activity, about 10.5-fold and 12-fold lower than those of Imatinib respectively. These results suggest that compound 13f is a promising candidate as a novel BCR-ABL kinase inhibitor for further development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
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Acrilamidas
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Desenho de Fármacos
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Proteínas de Fusão bcr-abl
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Inibidores de Proteínas Quinases
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article