Discovery and characterization of the N-phenyl-N′-naphthylurea class of p38 kinase inhibitors

Abstract An effort aimed at exploring structural diversity in the N -pyrazole- N ′-naphthylurea class of p38 kinase inhibitors led to the synthesis and characterization of N -phenyl- N ′-naphthylureas. Examples of these compounds displayed excellent inhibition of TNF-α production in vitro, as well as efficacy in a mouse model of lipopolysaccharide induced endotoxemia. In addition, perspective is provided on the role of a sulfonamide functionality in defining inhibitor potency.