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 groups on the anticonvulsant activities of N-Cbz-.alpha.-aminosuccinimides, various (R)- and (S)-N-alkyl substituted N-Cbz-.alpha.-aminosuccinimides (1 and 2) were prepared from the corresponding (R)- and (S)-N-Cbz-aspartic acid by using known reaction and were evaluated the anticonvulsant 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) $(ED_{50}=52.5 mg/kg, Pl=3.2)$. And in case of the PTZ test, (R)-N-Cbz-.alpha.-amino-N-ethylsuccinimide (1c) was the most active compound $(ED_{50}/=32.5mg/kg, Pl=3.1)$. The order of anticonvulsant activities of these compounds against the MES test, as judged from the ED_50values for the R series (1), was N-methyl > N-isobutyl > non-substituted > N-ethyl, N-allyl > N-benzyl compound; for the S series (2) N-methyl > N-altyl > non-substituted > N-isobutyl > N-ethyl > N-benzyl compound. The anticonvulsant activities in the PTZ tests of these compounds exhibited somewhat different pattern ; for the R series (1) Nethyl > N-methyl > N-isobutyl> non-substituted > N-allyl > N-benzyl 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.