NON-CARBOXYLIC ANTIINFLAMMATORY COMPOUNDS .3. N-(4,6-DIMETHYLPYRIDIN-2-YL)ARYLCARBOXAMIDES AND ARYLTHIOCARBOXAMIDES ACTING AS BRAIN EDEMA INHIBITORS

Pharmacomodulation of the non-carboxylic NSAID N-(4,6-dimethylpyridin- 2-yl)benzamide 1 led to the synthesis of structurally related furan, t hiophene and pyrrole carboxamides 3-14. The derivatives benzenethiocar boxamides 15-18 and heteroaryl-thiocarboxamides 19-22 were also prepar ed by oxygen/sulfur exchange; this reaction was more efficiently carri ed out by P4S10 than by Lawesson's reagent. The 20 synthesized compoun ds were evaluated against peripheral edema by a foot-pad carrageenin-i nduced edema test. Amides 3-5, 8, 9, 11, 12 and 14 were most active, e xhibiting > 90% inhibition after oral administration of 0.8 mmol . kg( -1). Two amides, 3 and 5, were selected for evaluation of their inhibi tory activity in PLA(2)-induced brain edema and were found to be more potent than dexamethasone after LP administration.