THE EFFECT OF N-SUBSTITUTED ALKYL-GROUPS ON THE ANTICONVULSANT ACTIVITIES OF N-CBZ-ALPHA-AMINO-N-ALKYLSUCCINIMIDES

For the purpose of defining the effects of the N-substituted alkyl gro ups on the anticonvulsant activities of N-Cbz-alpha-aminosuccinimides, various (R)- and (S)-N-alkyl substituted N-Cbz-alpha-aminosuccinimide s (1 and 2) were prepared from the corresponding (R)- and (S)-N-Cbz-as partic acid by using known reaction and were evaluated the anticonvuls ant activies in the MES and PTZ tests, including their neurotoxicities . The most active compound in the MES test was (R)-N-Cbz-alpha-amino-N -methylsuccinimide (1b) (ED(50)=52.5 mg/kg, PI=3.2). And in case of th e PTZ test, (R)-N-Cbz-alpha-amino-N-ethylsuccinimide (1c) was the most active compound (ED(50)=32.5 mg/kg, PI=3.1). The order of anticonvuls ant activities of these compounds against the MES test, as judged from the ED(50) values for the R series (1), was N-methyl > N-isobutyl > n on-substituted > N-ethyl, N-allyl > N-benzyl compound; for the S serie s (2) N-methyl > N-allyl > non-substituted > N-isobutyl > N-ethyl > N- benzyl compound. The anticonvulsant activities in the PTZ tests of the se compounds exhibited somewhat different pattern; for the R series (1 ) N-ethyl > N-methyl > N-isobutyl > non-substituted > N-allyl > N-benz yl compound in order of decreasing activity; for S series (2) N-ethyl > N-allyl, non-substituted > N-isobutyl > N-methyl > N-benzyl compound in order of decreasing activity.