Novel triazin-5-ones as potential antiseizure medicines

Novel triazin-5-ones as potential antiseizure medicines Anxiety and related issues are major health and social concerns in developed countries, affecting 10–20% of the population. The lowest effective inhibitory concentrations for GABA-AT were observed for two compounds: 3h (30.50±0.61 µM) and 3r (44.76±0.49 µM). Their IC50 values were similar to those of lamotrigine. In vitro tests showed that compounds 3h and 3f had the lowest IC50 values for GABA-AT inhibition, at 30.50±0.61 and 44.58±0.54, respectively. The anticonvulsant activity of 6-(4-methoxybenzyl)-3-R-4H-[1,2,4] triazin-5-ones in a corral seizure model depends on modifications to substituents at positions three and six of the heterocyclic 1,2,4-triazine ring. Leading compounds, 3f (3-(4-Chlorophenylamino)-6-(4-methoxybenzyl)-4H-[1,2,4]triazin-5-one) and 3h (3-(2,3-Dimethylphenylamino)-6-(4-methoxybenzyl)-4H-[1,2,4]triazin-5-one), completely inhibit clonic and tonic-clonic seizures. Compound 3r, which contains both tryptamine and triazine fragments, has a clear pharmacophore structure. However, the spatial structure of the pharmacophore in compound 3h, with the lowest binding energy to GABAa and GABA-AT and the best performance in tests, is not yet fully understood.