Epilepsy is the most frequent nearological affiction and afflicts 1% about of the world's population. Currently there is an urgent need for the development of novel anticonvulsants with higher levels of potency and lower levels of toxicity. In this paper, a series of new 6-(substituted-phenyl)thiazolo[3,2-b][1,2,4]triazole derivatives were synthesized and tested for their anticonvulsant activities using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (PTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. In these compounds, 6-(4-fluorophenyl)thiazolo[3,2-b][1,2,4]triazole (3c) showed selective protection against the MES seizures with an ED50 value of 49.1 mg/Kg and a TD50 value of 94.1 mg/Kg, which provided compound 3c a protective index (PI = TD50/ED50) of 1.9 in the MES test. 6-(4-Propoxyphenyl)thiazolo[3,2-b][1,2,4]triazole (5b) was found to be active in both models, i.e. MES test and PTZ test. In the PTZ screen, compound 5b gave an ED50 of 63.4 mg/Kg and a TD50 of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine.
Keywords: Anticonvulsant; Maximal electroshock; Pentylenetetrazole; Synthesis; Thiazolotriazole.