Structural modification studies of 3‐piperonylsydnone I. synthesis of piperonyl‐substituted pyrazoles, isoxazoles, triazoles, oxadiazoles and thiadiazoles

Abstract

As a structural modification study of the antimalarial compound 3‐piperonylsydnone, a number of pyrazoles, isoxazoles, 1,2,4‐triazoles, ψ‐1,2,4‐triazoles, 1,3,4‐oxadiazoles, 1,3,4‐thiadiazoles and their intermediates all of which contain the piperonyl moiety have been synthesized. The antimalarial activity of these compounds was found to be less than that of the original sydnone. With the exception of 2,4‐diamino‐5‐piperonylpyrimidine, among the compounds tested, those which showed survival time of eleven days or over all possess a N‐N linkage.

Mesoionic Sydnone: A Review in Their Chemical and Biological Properties

“…It was found that the N-N bond is essential for the antiplasmodial activity either in the sydnone or in the piperonyl moiety as highlighted in structures LIV-LVII. However, 3-piperonylsydnone was still the most active molecule among all tested compounds [81]. On the other hand, 4,4-bis (acetamidophenyl) sulfone derivatives were very potent antimalarial agents, while sydnone rendered it less active or inactive when they were combined in one structure LVIII [82].…”