SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF DERIVATIVES STRUCTURALLY RELATED TO NIMESULIDE

The present work reports the synthesis of a series of compounds struct urally related to the antiinflammatory and antihistaminic agent nimesu lide (I), in which the p-nitrophenyl moiety has been replaced by pyrid ine (1a-c) and pyridine N-oxide (2a-c). In addition, two compounds (3a , 4a) have been synthesized in which the p-nitro group of I was substi tuted by a cyano and a 1H-tetrazol-5-yl group, respectively. Represent ative 1a and 2a were also modified by replacing the methanesulfonamido group with an acetamido group (5a, 6a). The pharmacological evaluatio n of compounds 1-6 in comparison to I, indicates that such modificatio ns are detrimental to the activity. Moreover 3a and 4a caused bronchoc onstriction and hypotension, thus behaving as histaminic-like rather t hen antihistaminic agents.