Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A.
Bioorg Med Chem
; 26(22): 5852-5869, 2018 12 01.
Article
en En
| MEDLINE
| ID: mdl-30401502
ABSTRACT
Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenoles
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Proteínas Tirosina Quinasas
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Proteínas Serina-Treonina Quinasas
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Inhibidores de Proteínas Quinasas
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Compuestos Heterocíclicos
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article