The effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-amino-N-methylsuccinimides.
In connection with the development of new anticonvulsant agents with a broad spectrum, we found that N-Cbz-alpha-amino-N-alkylsuccinimides 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-alpha-amino-N-methylsuccinimide were prepared from N-Cbz-aspartic acid and were evaluated with their anticonvulsant activities against the MES and PTZ tests, in order to define the effect of N-substituted alkoxy carbonyl group with the anticonvulsant activities. From these studies, it was found that all the tested N-alkoxycarbonyl-alpha-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-alpha-amino-N-methyl-succinimide. 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-nitrobenzyloxycarbonyl > N-ethoxycarbonyl > 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 activities of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides.
Jung
K
K
College of Pharmacy, Kyungsung University, Pusan, Korea.
Son
K
K
Kim
M
M
Lee
J
J
Choi
J
J
Lee
E
E
Park
M
M
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000927:Anticonvulsants; D013388:Succinimides