Synthesis of novel 4-substituted and spiroglutarimide derivatives as potential anticonvulsants, sedatives and analgesics

ABSTRACT

New 2,6-piperidinediones 2[a-g] and 4[a-d] were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give alpha-cyanocinnamides 1[a-g] or cyclo-alkylidenes 3[a,b] which underwent Michael addition with ethyl cyanoacetate or diethylmalonate. Compounds 4[a-d] were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5[a-m]. Some new selected compounds 2[a-c,f] and 4[a-d] and 5[e,h,j] were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2[f]