Synthesis And Studies On Anticonvulsant Activity Of5-alkoxy-[1,2,4]triazolo[4,3-a]pyridine Derivatives

In this study, a series of5-alkoxy-[1,2,4]triazolo[4,3-a]pyridine derivatives were designed and synthesized.2,6-Dichloro pyridine as the starting material, we got the target compound3a-3s after hydrazine reaction, cyclization and alkylation reaction. Their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock test and the rotarod test, respectively. The results showed that compounds3d,3n,3o,3p and3s had anticonvulsant effects at low dose of30mg/kg, and their median effective dose (ED50) and median toxicity dose (TD50) were tested to get the quantitative evaluation. The most promising compounds3p (5-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridine) and3r (5-(4-bromophenoxy)-[1,2,4]triazolo[4,3-a] pyridine) showed a ED50of13.2and15.8mg/kg, and had protective index value of4.8and6.9, respectively. Anticonvulsant activity and protection index were better than those of the control drugs Phenobarbital (ED50=21.8, PI=3.2). For explanation of the putative mechanism of action, compound3p and3r was tested in chemical induced models. The results revealed that compound3p and3r was effective against the seizures induced by pentylenetetrazole, isoniazid,3-mercaptopropionic acid and thiosemicarbazide.