The effect ofN-alkyloxycarbonyl group on the anticonvulsant activities ofN-alkyloxycarbonyl-α-amino-N-methylsuccinimides.

Abstract

In connection with the development of new anticonvulsant agents with a broad spectrum, we found thatN-Cbz-α-amino-N-alkylsuccinimides showed significant anticonvulsant activities, and the pharmacological activities of these compounds were dependent on their stereochemistry andN-substituted alkyl group. These results prompted us to define the effects of other functional group on the anticonvulsant activities of these compounds. Therefore a series ofN-alkoxycarbonyl-α-amino-N-methylsuccinimide were prepared fromN-Cbz-aspartic acid and were evaluated with their anticonvulsant activities against the MES and PTZ tests, in order to define the effect ofN-substituted alkoxy carbonyl group with the anticonvulsant activities. From these studies, it was found that all the testedN-alkoxycarbonyl-α-amino-N-methylsuccinimides exhibited significant anticonvulsant activities in the PTZ test and were not active in the MES test. The most active compound in the PTZ test was (S)N-ethoxycarbonyl-α-amino-N-methylsuccinimide. We found that the pharmacological activities in the PTZ test were dependent on theirN-alkoxycarbonyl groups. They follow as such; The order of anticonvulsant activities for (R) series as evaluated by ED50 wasN-phenoxycarbonyl=N-4-nitrobenzyloxycarbonyl>N-ethoxycarbonyl >N-allyloxycarbonyl>N-tert. butoxycarbonyl compound; For the (S) seriesN-ethoxycarbonyl >N-phenoxycarbonyl>N-allyloxycarbonyl compound. From the above results, it was conceivable thatN-substituted alkoxycarbonyl group had certain effects on the anticonvulsant activities ofN-alkoxycarbonyl-α-amino-N-methylsuccinimides.