Discovery of imidazo[1,2- b]pyridazine derivatives as IKKβ inhibitors. Part 1: Hit-to-lead study and structure–activity relationship

Abstract

Imidazo[1,2- b]pyridazine derivatives from high-throughput screening were developed as IKKβ inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2- b]pyridazine scaffold, cell-free IKKβ inhibitory activity and TNFα inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure–activity relationship was revealed and the interaction model of imidazo[1,2- b]pyridazine compounds with IKKβ was constructed.