The Effect of N-Alkyloxycarbony Group on the Anticonvulsant Activities of N-Alkyloxycarbonyl-α-amino-N-methylsuccinimides = N-Alkyloxycarbonyl-α-aminogl tarimides의 항경련활성에 대한 N-Alkyloxycarbonyl Group의 영향

다국어 초록 (Multilingual Abstract)

In connection with the development of new anticonvulsant agents with a broad spectrum, we found that N-Cbz-α-amino- N-aIkylsuccinimides showed significant anticonvulsant activities, and the pharmacological activities of these compounds were dependent on their stereochemistry and N-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 of N-alkoxycarbonyl-α-amino-N-methylsuccinimide were prepared from N-Cbz-aspartic acid and were evaluated with their anticonvulsant activities againt the MES and PTZ tests, in order to define the effect of N-substituted alkoxy carbonyl group with the anticonvulsant activities. From there studies, it was found that all the tested N-alkoxycarbonyl-α-amino-N-methylsuccinimides exhibited significant anticonvulsant activities in the PTZ test and were not active in the MIS test. The most active compound in the PTZ test was (S) N-ethoxycarbonyl-α-amino-N-methyl-succinimide. We found that the pharmacological activities in the PTZ test were dependent on their N-alkoxycarbonyl groups. They fellow as such: The order of anticonvulsant activities for (R) series as evaluated by ED­(50) was N-phenoxycarbonyl=N-4-nitrobenzyloxycarbonyl > N-ethoxycarbonyi > N-allyloxycarbonyl > N-tert. butoxycarbonyl compound; for the (S) series N-ethoxycarbonyl > N-phenoxycarbonyl > N-allyloxycarbonyl compound. From the above results, it was conceivable that N-substituted alkoxycarbonyl group had certain effects on the anticonvulsant activiti es of N-a1koxycarbonyl-α-amino-N-methylsuccinimides.