Synthesis And Anticonvulsant Activity Evaluation Of7-Alkoxy[1,2,4]Triazolo[3,4-b]Benzothiazol-3(2H)-O NES

Aim To discover anticonvulsant medicine with higher activity and lower toxicity. A series of7-alkoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-ones were synthesized starting with6-methoxy-2-amino-benzothiazole. These compounds were identified with’H-NMR, MS and IR spectra. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicities were evaluated by the rotarod neurotoxicity test (Tox.). Among the twenty-two compounds synthesized, the anticonvulsant activity of7-propoxy[1,2,4]triazolo[3,4-b] benzothiazol-3(2H)-one is the best with ED50value of11.36mg/kg (9.85～13.11mg/kg), but its protective index (PI, PI=TD50/ED50) is low(8.45). We also found that7-butoxy[1,2,4]triazolo[3,4-b] benzothiazol-3(2H)-one has good anticonvulsant activity, with ED50value of13.63mg/kg (11.81～15.72mg/kg) and protective index value of49.07. The oral activity data of compound4d further confirmed its efficacy, in an anti-MES test, and high safety with a PI value of50.2. This value was by far superior to that provided by the standard drug carbamazepine (PI=11.1). To explain the possible mechanism of anticonvulsant activity, the compound4d was tested in pentylenetetrazole (PTZ),3-mercaptopropionic acid (3-MP) and Bicuculline (BIC) induced seizures tests, respectively. The results suggest that compound4d exerts anticonvulsant activity through GABA-mediated mechanism.