Synthesis biological evaluation and molecular modelling of 24-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors

摘要

A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1 -imidazoles, , , and 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 CONH substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor . Docking model of ALK5 in complex with showed that it fitted well in the ATP-binding pocket with favourable interactions.