Discovery of wrightiadione as a novel template for the TrkA kinase inhibitors.
Bioorg Med Chem Lett
; 25(22): 5186-9, 2015 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-26442778
ABSTRACT
Enzymatic kinase assays and docking simulation studies have shown that the natural product wrightiadione displays inhibitory activity toward TrkA and PLK3. In this study, the template of wrightiadione served as a starting point for Trk inhibitor development campaigns. Molecular simulation provided structural insights for the design of derivatives that were efficiently generated by our recently developed 3-step tandem synthetic approach, resulting in the discovery of compound 2h with biochemical potency at the single-digit micromolar level.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Receptor trkA
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Inibidores de Proteínas Quinases
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Indenos
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Isoflavonas
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article