SYNTHESIS, CHARACTERIZATION AND PHARMACOLOGICAL EVALUATION OF SOME NEW 6-(3,5-SUBSTITUTED-2-BROMO/HYDROXY PHENYL)-1,2,4-TRIAZINE DERIVATIVES AS ANTICONVULSANT AGENTS

6-(2-Amino-3,5-substituted phenyl)-1,2,4-triazines were prepared by refluxing semicarbazones or thiosemicarbazones in presence of sodium hydroxide solution. 6-(3,5-Substituted-2-bromophenyl)-1,2,4-triazine derivatives and 6-(3,5-substituted-2-hydroxyphenyl)-1,2,4-triazine derivatives were prepared from 6-(2-amino-3,5-substituted phenyl)-1,2,4-triazine derivatives by sodium nitrite, hydrobromic acid, copper (I) bromide and sodium nitrite, sulfuric acid, respectively. The structures of the synthesized compounds were confirmed on the basis of their elemental analysis and spectral data (FT-IR and H¹-NMR). Amongst synthesized compounds, some displayed significantly active profile against the electrically induced seizures at a dose of 30 mg/kg after 0.5 h. At the same dose level, one compound also showed activity after 4.0 h. Two compounds exhibited protection at dose level of 100 mg/kg after 0.5 h. At 4.0 h, two compounds persisted to reveal anti-MES protection at same dose, whereas two other compounds indicated to prevent seizure spread at a higher dose of 300 mg/kg after 4h. One compound displayed protection at 300 mg/kg after 0.5 h. The neurotoxicity screening data revealed that two compounds were exhibited neurotoxicity at a dose level of 300 mg/kg after 0.5 h. Screened compounds displayed 40.59, 56.88 and 66.61 % increase in immobility time. Some compounds showed excellent anticonvulsant activity with no neurotoxicity and little CNS depressant effect and does not violated Lipinski’s rule, making them potentially promising agents for treatment of epilepsy