Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors.
J Enzyme Inhib Med Chem
; 35(1): 702-712, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-32164459
ABSTRACT
A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles, 7a-c, 11a-h, and 16a-h has been synthesised and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Incorporation of a quinoxalin-6-yl moiety and a methylene linker at the 4- and 2-position of the imidazole ring, respectively, and a m-CONH2 substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor 11e. Docking model of ALK5 in complex with 11e showed that it fitted well in the ATP-binding pocket with favourable interactions.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteínas Quinases
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Receptor do Fator de Crescimento Transformador beta Tipo I
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Imidazóis
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article