Benzothiazole based inhibitors of p38α MAP kinase

Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38α MAP kinase are described. The issue of metabolic instability associated with vicinal phenyl, benzo[d]thiazol-6-yl oxazoles/imidazoles was addressed by the replacement of the central oxazole or imidazole ring with an aminopyrazole system. The proposed binding mode of this new class of p38α inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38α enzyme.

Graphical abstractThe rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38α MAP kinase are described.Figure optionsDownload full-size imageDownload as PowerPoint slide