Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2-α]pyridines derivatives as protein kinase inhibitors

We report here the synthesis, the biological evaluation and the molecular modeling studies of new imidazo[1,2-alpha]pyridines derivatives designed as potent kinase inhibitors. This collection was obtained from 2-aminopyridines and 2-bromoacetophenone which afforded final compound in only one step. The bioactivity of this family of new compounds was tested using protein kinase and ATP competition assays. The structure-activity relationship (SAR) revealed that six compounds inhibit DYRK1A and CLK1 at a micromolar range. Docking studies provided possible explanations that correlate with the SAR data. The most active compound 4c inhibits CLK1 (IC50 of 0.7 mu M) and DYRK1A (IC50 of 2.6 mu M). (C) 2016 Elsevier Masson SAS. All rights reserved.