N-Acyl-alpha-aminoglutarimide 계 화합물의 항경련 활성에 대한 N-Acyl 기의 영향

The effect of N-Acyl Groups on the Aniticonvulsant Activities of N-Acyl-alpha-amino-N-mehtyglutarimides

For the purpose of defining the effects of N-acyl groups on the anticonvulsant activities of N-acyl-alpha-glutarimides, various (R)- and (S)-N-acyl-alpha- aminoglutarimide were prepared from the corresponding N-Cbz-glutamic acid and were evaluated their anticonvulsant activies in the MES and PTZ test, including their neurotoxicities. Among the tested compounds, only (R) N-cinnamoyl-alpha-amino-N-meth- ylglutarimide showed anticonvulsant activity in the MES and PTZ test. And the other tested compounds was active in the only PTZ test. The order of anticonvulsant activities in the PTZ test was as followes ; for the (R) series, N-4-methoxycinnamoyl = cinnamoyl > N-4-nitrobenzoyl > N-benzoyl > N-phenylacetyl ; for the (S) series, N- 4- methoxycinnamoyl = N-3-nitrobenzoyl > N-4-nitrobenzoyl = N-cinnamoyl = N- phenylacetyl. From the above results, it was conceivable that the substituted N-acyl group had important effects on the anticonvulsant activites of these compounds. However steroisomeric deferences in the anticonvulsant activities were not exhibited clearly.