Central Depressant effects of N^3-Substituted 6-Azauridines in Mice

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Central depressant effects in mice of N^3-substituted 6-azauridines (6-AzUd) (1) were examined by intracerebroventricular (i.c.v) injection. Eleven derivatives including alkyl-, benzyl-, xylyl- and phenylethly-substitution onto the N^3-position of 1 were synthesized and their pharmacological effects were evaluated using hypnotic activity, locomotor activity, motor incoordination and pentobarbital-induced sleep prolongation as indices. Six of 12 compounds showed the hypnotic activity. At a dose of 2 μmol/mouse, the mean sleeping time induced by 1,N^3-benzyl-6-AzUd (7), N^3-o-xylyl-6-AzUd (8), N^3-m-xylyl-6-AzUd (9), N^3-p-xylyl-6-AzUd (10) and N^3-α-phenylethyl-6-AzUd (11) was 14,11,45,12,9 and 16 min, respectively. These derivatives and N^3-β-phenylethyl-6-AzUd (12)(1.5 μmol/mouse) significantly prolonged pentobarbital-induced (40 mg/kg, i.p.) sleeping time, whereas none of the N^3-alkylated derivatives (methyl-, ethyl-, n-propyl-, n-butyl- and allyl-substitution) exetred the hypnotic activity or pentobarbital-induced sleep prolongation. Nucleoside 1 and its xylyl-derivatives (1.5 μmol/mouse) singificantly decreased locomotor activity of mice, their effects paralleled the hypnotic activity. These compounds (1.5 μmol/mouse) also produced motor incoordination and potentiated the effect of diazepam-induced motor incoordination. These results indicate that 1 and its benzyl-related derivatives, but not alkyl-derivatives have a depressant effect on the central norvous system.
公益社団法人日本薬学会の論文
1991-10-25

Central Depressant effects of N^3-Substituted 6-Azauridines in Mice

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