Synthesis of novel 4-substituted-7-trifluoromethylquinoline derivatives with nitric oxide releasing properties and their evaluation as analgesic and anti-inflammatory agents

Six derivatives of the general formula 2- or 4-(7-trifluoromethylquinolin-4-ylamino) benzoic acid N′-(nitrooxyacetyl or propionyl) hydrazide and an oxime of the formula 1-[4-(7-trifluoromethylquinolin-4-ylamino)phenyl]ethanone oxime were synthesized and tested for their in vivo anti-inflammatory, analgesic, and ulcerogenic properties, as well as their in vitro nitric oxide release ability. Compound 2-(7-trifluoromethylquinolin-4-ylamino)benzoic acid N′-(2-nitrooxy propionyl)hydrazide 12 showed an anti-inflammatory activity comparable to that of indomethacin in the carrageenan-induced rat paw edema test, and equipotency to glafenine in the acetic acid mice induced writhing model at 100 mg/kg p.o., respectively. All the final compounds showed no tendency to induce stomach ulceration in rats; nitric oxide seems to contribute to their excellent safety profile.

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