Inhibitors of p38 kinase

Inhibition of p38 kinase is evolving as an approach to the discovery of new anti-inflammatory agents. Inhibitors of this enzyme modulate cytokine production, especially pro-inflammatory TNF-alpha and IL-1. These cytokines and others mediate a wide spectrum of diseases, notably rheumatoid arthritis. Cytokine modulators are expected to be disease modifying agents. The lead molecules disclosed in the patent literature fall into a class termed 1-pyridinyl-2-phenylazoles; this class of compounds encompasses promising drug candidates that are nonpeptide, orally active, of low molecular weight and selective for p38. Structural characteristics of inhibitors and p38 kinase background are discussed.