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 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.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. ahabadi@yahoo.com
Ashraf H
AH
Abadi
Gehan H
GH
Hegazy
Asmaa A
AA
El-Zaher
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013055:Spectrophotometry, Infrared
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011804:Quinolines; D009569:Nitric Oxide