Discovery of 2,4-1-Imidazole Carboxamides as Potent and Selective TAK1 Inhibitors.

Herein we report the discovery of 2,4-1-imidazole carboxamides as novel, biochemically potent, and kinome selective inhibitors of transforming growth factor β-activated kinase 1 (TAK1). The target was subjected to a DNA-encoded chemical library (DECL) screen. After hit analysis a cluster of compounds was identified, which was based on a central pyrrole-2,4-1-dicarboxamide scaffold, showing remarkable kinome selectivity.