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

作者：Ahuja Priya; Siddiqui Nadeem^*

来源：European Journal of Medicinal Chemistry, 2014, 80: 509-522.

DOI：10.1016/j.ejmech.2014.04.043

• Triazine
• Anticonvulsant
• Quantification
• Sodium channel
• GABA

A series of thirty indole C-3 substituted 5-amino-6-(5-substituted-2-phenyl-1H-indo1-1-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)-5fluoro-2-phenyl-1H-indol-3-yflethanone (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 gamma-amino butyric acid estimation was also performed on active compounds to perceive the mechanistic procedure responsible for it action.

• 出版日期2014-6-10