A New Class of Anticonvulsants Possessing 6 Hz Psychomotor Seizure Test Activity: 2-(1H-Benzotriazol-1-yl)-N '-[Substituted] Acetohydrazides

作者：Kumar Praveen^*; Tripathi Laxmi

来源：Medicinal Chemistry, 2012, 8(3): 337-348.

• Anticonvulsant
• Benzotriazole
• Computational study
• Docking study
• 6 Hz Psychomotor Seizure test
• Neurotoxicity

A series of 2-(1H-Benzotriazol-1-yl)-N'-[substituted]acetohydrazides was designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The new compounds were characterized using FT-IR, H-1 NMR, mass spectral data and elemental analysis. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The neurotoxicity was assessed using the rotarod method. The most active compound of the series was N'-[4-(1,3-Benzodioxol-5-yloxy)benzylidene]-2-( 1H-benzotriazol-1-yl)acetohydrazide (BTA 9), which showed good activity with 75 % protection (3/4, 0.5 h) at a dose of 100 mg/kg in mice. None of the compounds exhibited neurotoxicity. A computational study was carried out for the calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta, GABA (A) alpha-1 receptors and Na/H exchanger, in Lamarckian genetic algorithm based flexible docking studies.

• 出版日期2012-5