Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38α MAP kinase inhibitors with excellent in vivo antiinflammatory properties

Herein we report investigations into the p38α MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation.

Graphical abstractThe p38 MAP kinase activity of two series of trisubstituted imidazoles (X = C, N) is reported, leading to compounds with highly potent cellular and in vivo activity.Figure optionsDownload full-size imageDownload as PowerPoint slide