Synthesis of novel 4-substituted-7-trifluoromethylquinoline derivatives with nitric oxide releasing properties and their evaluation as analgesic and anti-inflammatory agents.
Bioorganic & medicinal chemistry 2005 Oct 15; 13(20):5759-65
Abadi A AH, Hegazy G GH, El-Zaher A AA
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. ahabadi@yahoo.com
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 100mg/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.