p38 Inhibitors: piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones

Abstract We have synthesized a series of C7-piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones that are highly potent inhibitors of both p38 MAP kinase activity and TNF-α release. The 4-aminopentamethylpiperidine naphthyridinone 5 , which was designed to block metabolism at major ‘hot spots’, combined excellent inhibitory potency with good oral bioavailability in the rat.