The effect of N-alkyloxycarbonyl group on the anticonvulsant activities ofN-alkyloxycarbonyl-alpha-amino-N-methylsuccinimides

In connection with the development of new anticonvulsant agents with a broa d spectrum, we found that N-Cbz-alpha-amino-N-alkylsuccinimides showed sign ificant anticonvulsant activities, and the pharmacological activities of th ese compounds were dependent on their stereochemistry and N-substituted alk yl group. These results prompted us to define the effects of other function al group on the anticonvulsant activities of these compounds. Therefore a s eries of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimide were prepared fro m N-Cbz-aspartic acid and were evaluated with their anticonvulsant activiti es againt the MES and PTZ tests, in order to define the effect of N-substit uted alkoxy carbonyl group with the anticonvulsant activities. From these s tudies, it was found that all the tested N-alkoxycarbonyl-alpha-amino-N-met hylsuccinimides exhibited significant anticonvulsant activities in the PTZ test and were not active in the MES test. The most active compound in the P TZ test was (S) N-ethoxycarbonyl-alpha-amino-N-methylsuccinimide. We found that the pharmacological activities in the PTZ test were dependent on their N-alkoxycarbonyl groups. They follow as such; The order of anticonvulsant activities for (R) series as evaluated by ED50 was N-phenoxycarbonyl=N-4-ni trobenzyloxycarbonyl>N-ethoxycarbonyl > N-allyloxycarbonyl > N-tert. butoxy carbonyl compound; For the (S) series N-ethoxycarbonyl > N-phenoxycarbonyl > N-allyloxycarbonyl compound. From the above results, it was conceivable t hat N-substituted alkoxycarbonyl group had certain effects on the anticonvu lsant activities of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides.