A Novel Pd-Catalyzed Cyclization Reaction of Ureas for the Synthesis of Dihydroquinazolinone p38 Kinase Inhibitors.

A series of potent p38 inhibitors based on the dihydroquinazoline scaffold was synthesized using a novel Pd-catalyzed cyclization reaction of aryl-benzyl ureas. Optimization of this compound class led to compound 20, which inhibits p38alpha in vitro with IC(50)=14 nM and is active in the mouse TNFalpha-release model.