Synthesis of new Mannich bases of arylpyridazinones as analgesic and anti-inflammatory agents


Gokce E., Bakir G., Sahin M., Kupeli E., Yesilada E.

ARZNEIMITTELFORSCHUNG-DRUG RESEARCH, vol.55, no.6, pp.318-325, 2005 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 6
  • Publication Date: 2005
  • Doi Number: 10.1055/s-0031-1296866
  • Title of Journal : ARZNEIMITTELFORSCHUNG-DRUG RESEARCH
  • Page Numbers: pp.318-325

Abstract

A series of 2-[[4-(substituted-phenyl/benzyl) -1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone derivatives was prepared and examined for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and H-1-NMR spectra and elementary analysis. Among the compounds prepared, 2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-6-(4-methoxy- phenyl)-3(2H)pyridazinone We was found to be a most promising analgesic and anti-inflammatory agent. Compound lVe showed more potent analgesic activity than acetylsalicyclic acid in the phenylbenzoquinone-induced writhing test. Also Me showed anti-inflammatory activity comparable to that of the standard compound indometacin against the carrageenan-induced paw edema. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed a gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. On the basis of the available data, the structureactivity relationship of the series of 2-[[4(substituted- phenyl/benzyl)-1-piperazinyl]methyl]-6- (4-methoxyphenyl)-3(2H) pyridazinones is also discussed.