Synthesis of new Mannich bases of arylpyridazinones as analgesic and anti-inflammatory agents.
A series of 2-[[4-(substituted-phenyl/ benzyl)-1-piperazinyllmethyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone derivatives was prepared and examined for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and 1H-NMR spectra and elementary analysis. Among the compounds prepared, 2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone IVe was found to be a most promising analgesic and anti-inflammatory agent. Compound IVe showed more potent analgesic activity than acetylsalicyclic acid in the phenylbenzoquinone-induced writhing test. Also IVe showed anti-inflammatory activity comparable to that of the standard compound indometacin against the carrageenan-induced paw edema. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed a gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. On the basis of the available data, the structure-activity relationship of the series of 2-[[4-(substituted-phenyl/benzyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H) pyridazinones is also discussed.
Gökçe
Mehtap
M
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey. mgokce@gazi.edu.tr
Bakir
Gökçen
G
Sahin
Mustafa Fethi
MF
Küpeli
Esra
E
Yeşilada
Erdem
E
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D016227:Benzoquinones; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005528:Foot / Q000473:pathology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D012997:Solvents; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D007202:Indicators and Reagents; D008352:Mannich Bases; D011724:Pyridazines; D012997:Solvents; C004532:quinone