Synthesis and neuropharmacological activity of some quinoxalinone derivatives

Abstract

Eight quinoxalinone derivatives were synthesized and investigated for some neuropharmacological effects (analgesia, sedation, convulsion, anxiety, memory and psychosis) in mice and rats. In the CNS
depressant activity, N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide is the most
active, while the other compounds appear variously dose-dependent. Only three of the compounds showed anxiolytic effect, with N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide
showing the highest activity at 2.5 mg/kg. At the dose of 30 mg/kg, 6-nitro-1,4-dihydroquinoxaline-2,3-dione showed a better anxiolytic effect in mice than diazepam (dose: 1 mg/kg), while 1,2,3,4-tetrahydroquinoxaline-2,3-dione (dose: 25 mg/kg) showed a comparative effect to diazepam. 6-Chloro-1,4-dihydro-quinoxaline-2,3-dione and N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamideshowed significant anticonvulsant action. None of the compounds showed any analgesic or antidopaminergic
effect. The LD50 (24 h) calculated for the compounds were between 74 and 160 mg/kg i.p.