K. Jung et al., The effect of N-alkyloxycarbonyl group on the anticonvulsant activities ofN-alkyloxycarbonyl-alpha-amino-N-methylsuccinimides, ARCH PH RES, 21(6), 1998, pp. 759-763
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.