Synthesis of 6-(4-(substituephenyl)pierazin)-3(2h)pyridazinone-2-yl morpholinoacetamide derivatives and investigation of their analgesic and antiinflamatory activities

In this present thesis new 6-[4-(substituephenyl)piperazine]-3(2H)pyridazinone-2-yl morpholinoacetamide (Va-f) derivatives have been synthesized and their analgesic and anti-inflammatory activities were evaluated. The structure of synthesized compounds were confirmed by their IR, 1H-NMR spectra and elementary analysis. The chemical structure and physicochemical data of the compounds have been given Table 4.The analgesic activity of 6-[4-(substituephenyl)piperazine]-3(2H)pyridazinone-2-yl morpholinoacetamide (Va-f) derivatives was determined by phenylbenzoquinon-induced writhing assay (PBQ test) and the anti-inflammatory activity was evaluated by carrageenan-induced rat paw edema model (CPE test). In analgesic activity test acetylsalicyclic acid (ASA) and in anti-inflammatory activity test indomethacine have been used as reference compounds. 6-[4-(2-Fluorophenyl)piperazine]-3(2H)pyridazinone-2-yl morpholinoacetamide Vd was shown to be more potent analgesic activity than acetylsalicyclic acid (ASA). Also Vd has shown anti-inflammatory activity close to indomethacin. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect.Furthermore 6-[4-(4-fluororophenyl)piperazine]-3(2H)pyridazinon-2-yl morpholinoacetamide Ve and 6-[4-(3-trifluoromethylphenyl)piperazine]-3(2H)piridazinon-2-yl morpholinoacetamide Vf derivatives have been shown significant analgesic and anti-inflammatory activities. It is well known that most of anti-inflammatory drugs provide an ulcerogenic activity. In the present experiment ASA and indometacin used as reference showed marked ulcerogenic effect. Thus it appeared that 6-[4-(2-fluorophenyl)piperazine]-3(2H)pyridazinon-2-yl morpholinoacetamide Vd possessed anti-inflammatory activity as well as indometacin and more potent analgesic activity than ASA and did not induce any gastric lesions or death the observation period.Pharmacological activity results of 6-[4-(substituephenyl)piperazine]-3(2H)pyridazinon-2-il morpholinoacetamide (Va-f) derivatives confirms that arylpiperazine moiety at position 6 of 3(2H)-pyridazinone ring influences analgesic and anti-inflammatory activities.Key Words: 3(2H)-pyridazinone, aryl piperazine, morpholinoacetamide, analgesic activity, anti-inflammatory activity.