Synthesis And Evaluation Of The Antiepileptic And The Antidepressant Activities Of5-Alkyl Thio-4-Benzyl Triazolones And Triazole-Containing Quinolinones

This paper designed and synthesized5-alkylthio-4-benzyl triazolones and triazole-containing quinolinones, and then evaluated their anticonvulsant and antidepressant activities.In the first section,5-alkylthio-4-phenyl-2,4-dihydro-3H-1,2,4-triazol-3-ones (4a-4w) were synthesized using phenyl isothiocyanate through nucleophilic addition, nucleophilic substitution and Williamson reactions, we also screened for their anticonvulsant activity and neurotoxicity. Of these compounds,5-(heptylsulfanyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazol-3-one (4g) brought out the most potent level of activity with an ED50value of38.7mg/kg, a TD50value of633.7mg/kg and a superior protective index (PI) value of16.4in the maximal electroshock seizure screen, which showed more safety and reliable than the clinical medicine carbamazepine (TD50=76.1mg/kg, PI=6.45).In the next section,1-substituted-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydroquinolin-2(1H)-ones (5a-5s) were synthesized using3,4-dihydroquinolin-2(1H)-one through nitration, reduction, Williamson and triazole cyclization reactions, and evaluated their antiepileptic and antidepressant activities. Compounds5c and5d showed moderate levels of anticonvulsant activity and protected100%of the animals at a dose of100mg/kg. Specially, none of the synthesized compounds showed any neurotoxicity in the rotarod test at a dose of100mg/kg. In the forced swimming test, compounds5i,5j,5m and5n led to significant reductions in the immobility time at a dose of50mg/kg, and exhibited higher levels of efficacy than the reference standard fluoxetine. In addition, compound5i showed greater efficacy than fluoxetine in the tail suspension test. Therefore, l-substituted-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro quinolin-2(1H)-ones provided some original and significant meanings for the application of the anticonvulsant and antidepressant drugs.