K. Son et al., The effect of N-alkyloxycarbonyl group on the anticonvulsant activities ofN-alkyloxycarbonyl-alpha-aminoglutarimides, ARCH PH RES, 21(6), 1998, pp. 764-768
In connection with the development of new anticonvulsant agents with a broa
d spectrum, we reported that N-Cbz-alpha-aminoglutarimides, combining commo
n structures of other anticonvulsants such as N-CO-C-N and cyclic imides in
a single molecule, showed significant anticonvulsant activities in the MES
(maximal electroshock seizure) and PTZ (pentylenetetrazole induced seizure
) tests. In these studies, a series of (R) and (S) N-alkyloxycarbonyl-alpha
-aminoglutarimides 7a similar to 7e and 8a similar to 8e, which were substi
tuted with various alkyloxycarbonyl group instead of Cbz group, were prepar
ed from the corresponding (R) and (S) N-Cbz-glutamic acid 3 and 4, and were
evaluated with their anticonvulsant activities against the MES and PTZ tes
ts, including neurotoxicity, in order to define the effect of N-alkyloxycar
bonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-am
inoglutarimides. Among them, (3) N-4-nitrobenzyloxycarbonyl-alpha-amino-N-m
ethylglutarimide 8e was the most active in MES (ED50=35.6 mg/kg, PI=2.7) an
d PTZ tests (ED50= 15.6, PI=6.1). Interestingly, (R) and (S) N-4-nitrobenzy
loxycarbonyl-alpha-amino-N-methylglutarimide 7e and 8e and (R) N-phenoxycar
bonyl-alpha-amino-N-methylglutrimide 7d showed significant anti-convulsant
activities in both the MES and PTZ tests and other compounds showed anti-co
nvulsant activities in only the PTZ test In addition, it was found that the
ir anticonvulsant activities were dependent on their stereochemistries and
N-substituted alkyloxycarbonyl groups.