Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities.
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 l(a-g) or cycloalkylidenes 3(a,b) which underwent Michae1 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), 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).