Synthesis, characterization and preliminary anticonvulsant evaluation of some 4-alkyl-1,2,4-triazoles

Designed and synthesized 4-alkyl-1,2,4-triazole-3-thione derivatives showed significant anticonvulsant activity, determined in the maximal electroshock-induced seizure (MES) test. The chemical structure of all new compounds was confirmed by spectral methods (1H NMR, 13C NMR, IR, MS). A sensitive and selective method was elaborated for the determination of the anticonvulsant compounds levels in mice brain tissue, based on HPLC with diode array detector (DAD). Chromatographic tests showed that lack of anticonvulsant effect of two derivatives (15, 16) with long alkyl chains at N-4 position of the 1,2,4-triazole ring was due to the inability to cross the blood–brain barrier (BBB).

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► Alkyl derivatives of 1,2,4-triazoles were designed and synthesized.
► Anticonvulsant activity was up to 7-fold higher than that of valproate.
►  Concentration of the compounds in mice brain was measured by HPLC/DAD method.