Synthesis and anticonvulsant activity evaluation of 3-alkoxy-4-[4- [hexyloxy/heptyloxy]phenyl]-4H-1,2,4 -triazole

A series of 3-alkoxy-4-[4-[hexyloxy/heptyloxy] phenyl]-4H-1,2,4-triazole was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock [MES] test and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, compound 3-heptyloxy-4-[4-[hexyloxy] phenyl]-4H-1,2,4-triazole [5f] was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose [ED[50]] of 37.3 mg/Kg, median toxicity dose [TD[50]] of 422.5 mg/Kg, and the protective index [PI] of 11.3 which is much greater than the reference drug carbamazepine with PI value of 6.4. As well as demonstrating the anti-MES efficacy of compound 5f, its potency against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline were also established, with the results suggesting that GABA-mediated mechanisms might be involved in its anticonvulsant activity, such as enhancing of GABAergic neurotransmission or activity, activate GAD or inhibit GABA-T, and GABA[A]-mediated mechanisms

Synthesis and anticonvulsant evaluation of some new 6-[substituted-phenyl] thiazolo[3,2-b][l,2,4]triazole derivatives in mice

Epilepsy is the most frequent nearological affiction and afflicts 1% about of the worlds 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-phenyT] 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][l,2,4]triazole [3c] showed selective protection against the MES seizures with an ED[50] value of 49.1 mg/Kg and a TD[50] value of 94.1 mg/Kg, which provided compound 3c a protective index [PI = TD[50]/ED[50] of 1.9 in the MES test. 6-[4-Propoxyphenyl]thiazolo[3,2-b][l,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 ED[50] of 63.4 mg/Kg and a TD[50] of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine