Synthesis and pharmacological evaluation of derivatives structuraily related to nimesulide

Article abstract of DOI:10.1016/0223-5234(96)89162-8

The present work reports the synthesis of a series of compounds structurally related to the antiinflammatory and antihistaminic agent nimesulide (I), in which the p-nitrophenyl moiety has been replaced by pyridine (1a-c) and pyridine N-oxide (2a-c).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 substituted by a cyano and a 1H-tetrazol-5-yl group, respectively. Representative 1a and 2a were also modified by replacing the methanesulfonamido group with an acetamido group (5a, 6a). The pharmacological evaluation of compounds 1-6 in comparison to I, indicates that such modifications are detrimental to the activity. Moreover 3a and 4a caused bronchoconstriction and hypotension, thus behaving as histaminic-like rather then antihistaminic agents.