Pyridazine Based Inhibitors of p38 MAPK.

Abstract Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors of p38 MAPK. The most active isomers were those possessing an aryl group α and a heteroaryl group β relative to the nitrogen atom in the 2-position of the central pyridazine. Additionally, substitution in the 6-position of the central pyridazine with a variety of dialkylamino substituents afforded a set of inhibitors having good (p38 IC 50 1–20 nM) in vitro activity.