Synthesis and biological evaluation of N-antipyrine-4-substituted amino-3-chloromaleimide derivatives

This paper describes the synthesis of new cyclic imides obtained by reaction with N-antipyrine-3,4-dichloromaleimides and different aromatic amines. The analgesic activity of the synthesized compounds was initially investigated against the writhing test in mice, followed by analysis of the most promising compounds in this model and in the formalin-induced model. The results indicate that the compounds containing the electron-withdrawing substituents in the para position of the substitute ring exerted more potent analgesic activity in mice, being much more potent than the prototype N-antipyrine-3,4-dichloromaleimide and some reference drugs. Some compounds exhibited activity against human opportunistic and pathogenic fungi, with MIC values of between 40 and 100 μg/mL (91.74 and 236.96 μM), and it was verified that only a few compounds presented potential for cytotoxic activity.

Graphical abstractIn the present study, we have synthesized twenty-one N-antipyrine-4-substituted amino-3-chloromaleimide derivatives analogous to metamizole, and screened them for their antinociceptive, antimicrobial and cytotoxic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide