Synthesis and biological evaluation of benzenesulfonamide-substituted 4-(6-alkylpyridin-2-yl)-5-(quinoxalin-6-yl)imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors.

A series of benzenesulfonamide-substituted 4-(6-alkylpyridin-2-yl)-5-(quinoxalin-6-yl)imidazoles have been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 4-[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-ylmethyl]benzenesulfonamide and 4-[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-ylmethyl]benzenesulfonamide showed more than 90% inhibition at 0.5 microM in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct, but inhibited p38alpha MAP kinase activity only 11 and 8% at a concentration of 10 microM, respectively.