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Design, Synthesis and Anticonvulsant Activity Evaluation of 7-Substituted –[1,2,4]-Triazolo[4,3-f]Pyrimidine Derivatives

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In this study, a novel series of 7-substituted-[1,2,4]triazolo[4,3-f]pyrimidine derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that the compound 3i (7-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-f]pyrimidine) was among the most active agent with median effective dose (ED50) value of 34.7 mg/kg, median toxicity dose (TD50) of 262.9 mg/kg, and providing a protective index (PI=TD50 /ED50) value of 7.6. The compound 3i also showed oral activity against MES-induced seizures and lower oral neurotoxicity. The compound 3i demonstrated antagonistic activity against seizures induced by PTZ, ISN, 3-MP and thiosemicarbazide.
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Keywords: 3-MP; ISN; PTZ; Triazolo; anticonvulsant; maximal electroshock; neurotoxicity; pyrimidine; synthesis; thiosemicarbazide

Document Type: Research Article

Publication date: November 1, 2012

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