Synthesis and biological evaluation of 5-(pyridin-2-yl)thiazoles as transforming growth factor-β type1 receptor kinase inhibitors

Abstract: A series of 5-(pyridin-2-yl)thiazoles (14a–l and 15a–l) has been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 3-[[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl]benzamide (15i) and 3-[[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl]benzamide (15k) showed more than 95% inhibition at 0.1μM in luciferase reporter assays using HaCaT cells transiently transfected with p3TP-luc reporter construct and ARE-luciferase reporter construct. [Copyright &y& Elsevier]