Synthesis of 4(1H)-pyridinone derivatives and investigation of analgesic and antiinflammatory activities

This paper describes recent results of a research program aimed at the synthesis and pharmacological evaluation of new 4(1H)-pyridinone derivatives belonging to the 1,3-disubstituted series (4-11). These compounds were structurally planned by applying the molecular hybridization strategy on previously described 1,2-disubstituted-4(1H)-pyridinone derivatives, considered as lead compounds, which present potent analgesic properties (M.D. Aytemir, T. Uzbay, D.D. Erol, Arzneim. Forsch. (Drug Res.) 49 (1999) 250). Their chemical structures have been proved by means of their IR and H-1 NMR data and by elemental analysis. The analgesic profile of the title compounds (4-11), evaluated by the model of abdominal constrictions induced by acetic acid, showed that all the 4(1H)-pyridinone derivatives were active, exhibiting an analgesic Activity comparable with that of aspirin (acetyl salicylic acid) used as a standard. The antiinflammatory profile of the synthesized compounds, evaluated by the model of carrageenan rat paw edema, showed that all compounds were active and were comparable with indomethacin used as a standard. (C) 2001 Elsevier Science S.A. All rights reserved.