The synthesis of new isochromanylacetylarylhydrazones designed as probable non-addictive analgesic agents

• Autor(a) principal: Santos,Margareth Rôse L.
• Data de Publicação: 1997
• Outros Autores: Barreiro,Eliezer J., Braz-Filho,Raimundo, Miranda,Ana Luisa P.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50531997000500007
• topic: analgesic agents; isochromanylacetylarylhydrazones

The synthesis and pharmacological profile as analgesic and anti-inflammatory agents of new isochromanylacetylarylhydrazone derivatives (3) are described in this paper. The synthetic route used in this work to construct the heterocyclic six member ring explored a Lewis acid-catalyzed cyclization process as the key step, which represents a modified Friedel-Crafts reaction. These new derivatives (3) were obtained in ca. 85 % overall yields from the starting material safrole (4), an abundant natural product isolated from Sassafras oil. The NMR spectral analysis of these new derivatives indicated, at the C=N double bond level, the diastereomeric nature in a 70:30 ratio, where the major compound is the (E)-isomer. The results obtained from the pharmacological evaluation of (3) using the carrageenan-induced rat paw edema test and the acetic acid solution-induced constrictions in mouse test, indicated the pharmacophoric nature of the acylarylhydrazone moiety to the analgesic activity observed in this series.The role of the aryl substituents in the bioactivity seems to indicate that the presence of hydrophobic groups may improve the analgesic profile. These new isochromanylacetylarylhydrazone derivatives (3) represent a new class of non-addictive analgesic agents.