Synthesis and evaluation of the analgesic and anti-inflammatory activity of new 3(2H)-pyridazinone derivatives.
A series of 6-substituted-3(2H)-pyridazinone derivatives were synthesized and evaluated for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. Analgesic and anti-inflammatory activities of the title compounds have been evaluated. Four of the ten tested compounds possessed significant analgesic effects in the phenylbenzoquinone-induced writhing test (PBQ test). The most active derivatives 8a, 8b, 8d, 8e were void of gastric ulcerogenic effect or acute toxicity at the maximal dose (200 mg/kg p.o.). In the carrageenan-induced paw edema model, compound 8d (6- [4- (2-fluorophenyl) piperazin-1-yl]-3(2H)-pyridazinone) showed anti-inflammatory activity similar to that of the standard drug indometacin (CAS 53-86-1). A significant dependence of the anti-inflammatory effect on the substituents was observed; The pharmacological study of these compounds confirms that modification of the chemical group at position 6 of the 3(2H)-pyridazinone ring influences analgesic and anti-inflammatory activities.
Gökçe
Mehtap
M
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey. mgokce@gazi.edu.tr
Sahin
Mustafa Fethi
MF
Küpeli
Esra
E
Yeşilada
Erdem
E
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D001681:Biological Assay; D002351:Carrageenan; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011724:Pyridazines; D002351:Carrageenan