Synthesis And Anticonvulsant Activity Of 5-substituted-[1,2,4] Triazolo [4,3-α] Quinazolines

A series of 5-substituted-[1,2,4]triazolo[4,3-a]quinazolines was synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test with intraperitoneally injected in mice. The pharmacology results showed that 5-pentyloxy-[1,2,4]triazolo[4,3-a]quinazoline (2d) was the most potent with ED50 value of 19.7 mg/kg and protective index (PI= TD50/ED50) value of 6.2. To explain the possible mechanism of anticonvulsant activity, the compound 2d was tested in several chemical induced seizures tests. The results revealed that compound 2d was effective against the seizures induced by pentylenetetrazole, isoniazid,3-mercaptopropionic acid and thiosemicarbazide, which suggested that the anticonvulsant effects of this series compounds were worked via increasing GABAergic neurotransmission and activating glutamate decarboxylase (GAD) or inhibiting a-oxoglutarate aminotransferase (GABA-T) in the brain.