Synthesis and analgesic and anti-inflammatory activity of ethyl (6-substituted-3 (2H)-pyridazinone-2-yl)acetate derivatives.
A number of 6-substituted-3(2H)-pyridazinones and the corresponding methyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate derivatives carrying the arylpiperazinyl structure present in potent antinociceptive agents reported in the literature were synthesized. As part of a programme a series of diverse arylpiperazine derivatives of ethyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate were prepared and tested for their in vivo analgesic and anti-inflammatory activity by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with reference non-steroidal anti-inflammatory drugs (NSAIDs). On the basis of available data, the structure-activity relationship in the series of ethyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate derivatives was also discussed. When compared to parent 6-substituted-3(2H)-pyridazinones, the new ester derivatives, for example ethyl (6-4-[(2-fluoro)phenyl]piperazine-3(2H)-pyridazinone-2-yl)acetate exhibited better analgesic and anti-inflammatory activity and a lower ulcerogenic effect.
Dündar
Yasemin
Y
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Hipodrom-Ankara, Turkey.
Gökçe
Mehtap
M
Küpeli
Esra
E
Sahin
Mustafa Fethi
MF
D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D016227:Benzoquinones; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012997:Solvents; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology
D000085:Acetates; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D007202:Indicators and Reagents; D011724:Pyridazines; D012997:Solvents; C004532:quinone; D002351:Carrageenan