A NOVEL SYNTHESIS AND POTENT ANTIINFLAMMATORY ACTIVITY OF 4-HYDROXY-2(1H)-OXO-1-PHENYL-1,8-NAPHTHYRIDINE-3-CARBOXAMIDES

New antiinflammatory agents 4-hydroxy-2(1H)-oxo-1-phenyl-1,8-naphthyridine-3-carboxamides 7 were designed and synthesized via a valuable intermediate, 1-phenyl-2H-pyrido[2,3-d][1,3]oxazine-2,4(1H)-dione (9). The nature of substituents on the amide nitrogen had a pronounced effect on antiinflammatory activity. Studies of structure-activity relationships led to compounds 33 and 34 bearing a pyridine ring on the amide nitrogen. Compounds 33 and 34 were active against carrageenin-, zymosan-, and arachidonic acid-induced rat paw edemas and also potently inhibited the reversed passive Arthus reaction in rats. Thus, they possess a broader spectrum of antiinflammatory activity than the classical nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin and piroxicam.