Synthesis and Analgesic and Anti-inflammatory Activity of Ethyl (6-Substituted-3(2H)-pyridazinone-2-yl)acetate Derivatives

Abstract

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.