Design, synthesis and preliminary evaluation of some novel [1,4]diazepino [5,6-b]pyrrolizine and 6-(2-oxopyrrolidino)-1H-pyrrolizine derivatives as anticonvulsant agents

New series of diazepino[5,6-b]pyrrolizines 7a-c and 8a-c and 6-(2-oxopyrrolidino)-1H-pyrrolizines 10a-c were synthesized through acylation of the key aminonitrile derivatives 5a-c (Scheme 1) with the appropriate acid chlorides. Subsequent cyclization reaction yielded the target compounds (Schemes 2, 3). The chemical structure of the synthesized compounds was elucidated by spectral and elemental analyses. The synthesized compounds were evaluated for their ability to protect mice against PTZ-induced seizures, the most active compounds were 10a-c where compound 10b exhibited 67.9% relative potency compared to phenobarbitone and compound 10a provided the maximum protection % of all compounds (60%) at dose of 50 mg/kg comparable to phenobarbitone at a dose of 20 mg/kg.