Preparation and antiinflammatory activity of 2- and 4-pyridones.
Several N-alkyl- and N-arylacetoacetamides have been self-condensed to form pyridones. N-Alkylacetoacetamides give 2-pyridones, while N-arylacetoacetamides give 4-pyridones. In an attempt to develop nonacidic, nonsteroidal antiinflammatory agents, the pyridones were tested in a carrageenan-induced pedal edema assay in rats. While the 2-pyridones were not active, 9 of 17 4-pyridones tested were active, and one compound (4g) had antiinflammatory efficacy in a dose-response assay (ED50 values). Most compounds were considered nontoxic by determination of approximate LD50 values in mice by a standard multidimensional observational assay.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D001169:Arthritis, Experimental / Q000188:drug therapy; D002351:Carrageenan / Q000037:antagonists & inhibitors; D055598:Chemical Phenomena; D002621:Chemistry; D007928:Lethal Dose 50; D008297:Male; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D011728:Pyridones; D002351:Carrageenan