Anticonvulsant evaluation of clubbed indole-1,2,4-triazine derivatives: A synthetic approach

• Indole-1,2,4-triazine derivatives were reported as potential anticonvulsant agents.
• 6b exhibited minimal duration of limb extension as 5.40 ± 0.61 s in MES test.
• 7b gave the seizure latency to onset of clonus >14 min in scPTZ test.
• ED50 of 6b in MES test is 7 mg/kg and of 7b in scPTZ test is 35 mg/kg.
• In vitro sodium channel assay and GABA estimation showed significant outcomes.

A series of thirty indole C-3 substituted 5-amino-6-(5-substituted-2-phenyl-1H-indol-1-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-thione 5a–f, 6a–f, 7a–f, 8a–f and 9a–f were synthesized to explore prospective anticonvulsant agents. The derivative 1-(1-(5-amino-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-5-fluoro-2-phenyl-1H-indol-3-yl)ethanone (6b) had significant activity in maximal electroshock test with minimal duration of limb extension (5.40 ± 0.61 s) and quantitative median dose of 7 mg/kg. In subcutaneous pentylenetetrazole screen 1-(5-amino-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-5-fluoro-2-phenyl-1H-indole-3-sulfonamide (7b) increased the seizure latency to onset of clonus and was effective at a median dose of 35 mg/kg. An in vitro radioligand binding assay on sodium channel and γ-amino butyric acid estimation was also performed on active compounds to perceive the mechanistic procedure responsible for it action.

Indole C-3 substituted 5-amino-6-(5-substituted-2-phenyl-1H-indol-1-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-thione 5a–f, 6a–f, 7a–f, 8a–f and 9a–f were synthesized considering the pharmacophoric elements and an array of functional groups necessary for anticonvulsant activity.Figure optionsDownload as PowerPoint slide