Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives

Twenty new 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) urea derivatives were designed and synthesized. Antiepileptic screening was performed using MES and scPTZ seizures tests. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 5c, 5g, 5j and 5n were found active in MES model, while 5o showed significant antiepileptic activity in scPTZ model. Further all these five compounds were administered orally to rats, 5c, 5g and 5n showed better activity than Phenytoin in oral route. Among these compounds 5c revealed protection in MES at a dose of 30 mg/kg and 100 mg/kg 0.5 h and 4 h after i.p. administration respectively. This molecule provided also protection in the scPTZ at a dose of 300 mg/kg in both time intervals.

Graphical abstractVarious 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives (5a–t) were synthesized and evaluated. Antiepileptic screening revealed some potential compounds that were active in both MES and scPTZ screenings.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel isatin derivatives were synthesized and evaluated for antiepileptic activity. ► Compounds 5c, 5g, 5j & 5n were active in MES while, 5o in scPTZ with no neurotoxicity. ► p-substitutes showed better protection in both models than other substitutes.