Synthesis and analgesic and antiinflammatory activity of methyl 6-substituted-3(2h)-pyridazinone-2-ylacetate derivatives.

Abstract

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 (1)H-NMR spectra and elemental analysis.

• Authors: M F Sahina, B Badiçoglu, M Gökçe, E Küpeli, E Yeşilada
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 337 Issue 8 Pg. 445-52 (Aug 2004) ISSN: 0365-6233 [Print] Germany
• PMID: 15293264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Analgesics, Non-Narcotic
• Anti-Inflammatory Agents, Non-Steroidal
• Pyridazines
• Carrageenan

Topics

• Acetates (chemical synthesis)
• Analgesics, Non-Narcotic (chemical synthesis, pharmacology, toxicity)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, pharmacology, toxicity)
• Carrageenan
• Edema (chemically induced, prevention & control)
• Male
• Mice
• Molecular Weight
• Pain Measurement (drug effects)
• Pyridazines (chemical synthesis, pharmacology)
• Stomach Ulcer (chemically induced)