Synthesis and Analgesic and Antiinflammatory Activity of Methyl 6-Substituted-3(2H)-pyridazinone-2-ylacetate Derivatives

A series of methyl 6‐substituted‐3(2H)‐pyridazinone‐2‐ylacetates 9 were synthesized and their analgesic and anti‐inflammatory effects were evaluated in the phenylbenzoquinone‐induced writhing test (PBQ test) and carrageenan‐induced paw edema method, respectively. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with reference nonsteroidal anti‐inflammatory drugs. Methyl 6‐(4‐(4‐fluorophenyl)piperazine)‐3(2H)‐pyridazinone‐2‐ylacetate 9e was found to be more active than acetylsalicylic acid (ASA). Methyl 6‐(4‐(2‐ethoxyphenyl)piperazine)‐3(2H)‐pyridazinone‐2‐ylacetate 9c has shown an anti‐inflammatory activity as compared to the standard compound indometacin at the carrageenan‐induced paw edema method. A significant dependence of the anti‐inflammatory effect on the substituents has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at the position 6 of the 3(2H)‐pyridazinone system influences analgesic and anti‐inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and 1H‐NMR spectra and elemental analysis.