Structure-based design, synthesis, andanticonvulsant activity of isatin-1-N-phenylacetamide derivatives

Article abstract of DOI:10.1007/s00044-013-0811-1

In an effort to develop the potent anticonvulsant agents, a series of novel isatin-1-N-phenylacetamide derivatives was synthesized and screened for their in vivo anticonvulsant activity against maximal electroshock test and evaluated for their neurotoxicity by the rotarod test at the same dose levels. Ten compounds exhibited the anticonvulsant activity. 2-(5-Methyl-2,3-dioxoindolin-1- yl)-N-phenylacetamide (4b) was found to be the most potent compound of the series with an ED₅₀ of 91.3 mg/kg, TD₅₀ of >1,000 mg/kg, a higher protective index (PI = TD₅₀/ED₅₀, >11) was gained than the reference drug phenobarbital and carbamazepine. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore. Springer Science+Business Media 2013.