RESUMEN
A series of 2-[[4-(substituted-phenyl/ benzyl)-1-piperazinyllmethyl]-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 1H-NMR spectra and elementary analysis. Among the compounds prepared, 2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone IVe was found to be a most promising analgesic and anti-inflammatory agent. Compound IVe showed more potent analgesic activity than acetylsalicyclic acid in the phenylbenzoquinone-induced writhing test. Also IVe 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 structure-activity relationship of the series of 2-[[4-(substituted-phenyl/benzyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H) pyridazinones is also discussed.
Asunto(s)
Analgésicos/síntesis química , Analgésicos/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/farmacología , Bases de Mannich/síntesis química , Bases de Mannich/farmacología , Piridazinas/síntesis química , Piridazinas/farmacología , Animales , Benzoquinonas , Edema/inducido químicamente , Edema/patología , Edema/prevención & control , Pie/patología , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Masculino , Bases de Mannich/toxicidad , Ratones , Contracción Muscular/efectos de los fármacos , Piridazinas/toxicidad , Solventes , Espectrofotometría Infrarroja , Úlcera Gástrica/inducido químicamente , Relación Estructura-ActividadRESUMEN
It is known that some addition products of beta-nitrostyrenes exhibit potent antimicrobial activity. In order to investigate the effects of structural modifications on the biological properties, some new Michael type addition products of beta-ethyl-beta-nitrostyrenes were synthesized. In this study, eight new 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane (2) derivatives were synthesized by addition of 2-aminothiophenol to the double bond of beta-ethyl-beta-nitrostyrenes (1). The chemical structures were proved by IR and 1H-NMR data and by elemental analysis. Antimicrobial activities of the synthesized compound were investigated against Escherichia coil, Pseudomonas aeruginosa, Proteus mirabilis, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Candida albicans by the microdilution method. In addition, the newly synthesized compounds were studied for antiviral activities. All of them were found to be almost 100 fold more active than the standard compound aciclovir (CAS 59277-89-3).