Synthesis of Dipyrone Metabolites and Evaluation of their Antipyretic Effect

Synthesis of Dipyrone Metabolites and Evaluation of their Antipyretic Effect

Vaz, Artur; Aguiar, Fernando A.; Malvar, David C.; Souza, Gloria E. P.; Clososki, Giuliano C.

Abstract:

Metamizole, or dipyrone (DIP), is a widely used prodrug (bioprecursor class) with powerful analgesic and antipyretic effects. In the gastrointestinal tract DIP is first hydrolyzed to 4-methylaminoantipirine (4- MAA), which is then absorbed and metabolized in the liver to the corresponding 4-aminoantipyrine (4- AA) and 4-formylamino-antipyrine (4-FAA) derivatives. Furthermore, the 4-AA suffers an acylation reaction to afford the 4- acetylaminoantipyrine (4-AAA). Despite some authors have proposed that 4-MAA and 4-AA are the active metabolites of dipyrone, the exact mechanism of action of these and other bioactive metabolites is still unknown. Thus, in this work we have synthesized the main metabolites of dipyrone and these have been used in studies that aims to compare their antipyretic effects in the fever induced by LPS and Tsv (Tityus serrulatus venom).

Metamizole, or dipyrone (DIP), is a widely used prodrug (bioprecursor class) with powerful analgesic and antipyretic effects. In the gastrointestinal tract DIP is first hydrolyzed to 4-methylaminoantipirine (4- MAA), which is then absorbed and metabolized in the liver to the corresponding 4-aminoantipyrine (4- AA) and 4-formylamino-antipyrine (4-FAA) derivatives. Furthermore, the 4-AA suffers an acylation reaction to afford the 4- acetylaminoantipyrine (4-AAA). Despite some authors have proposed that 4-MAA and 4-AA are the active metabolites of dipyrone, the exact mechanism of action of these and other bioactive metabolites is still unknown. Thus, in this work we have synthesized the main metabolites of dipyrone and these have been used in studies that aims to compare their antipyretic effects in the fever induced by LPS and Tsv (Tityus serrulatus venom).

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DOI: 10.5151/chempro-15bmos-BMOS2013_20139142095

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Como citar:

Vaz, Artur; Aguiar, Fernando A.; Malvar, David C.; Souza, Gloria E. P.; Clososki, Giuliano C.; "Synthesis of Dipyrone Metabolites and Evaluation of their Antipyretic Effect", p-12-12. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_20139142095