The 6-azauridine analogues possessing sedative and hypnotic effects.
Pharmacological effects of 6-azauridine (4) analogues were evaluated using hypnotic activity, pentobarbital (PB)-induced sleep prolongation and locomotor activity as indices. Compound 4, N3-benzyl- (10), N3-o-xylyl- (11), N3-m-xylyl- (12), N3-p-xylyl- (13), N3-alpha-phenylethyl-substituted 6-azauridine (14) exhibited hypnotic activity and PB-induced sleep prolongation, whereas N3-alkyl substituted analogues (methyl-, ethyl-, n-propyl-, n-butyl- and allyl-substitution) did not. Compound 4 and xylyl analogues (11-13) significantly decreased locomotor activity of mice by i.c.v. injection and produced motor incoordination. The results indicate that 4 and its benzyl related analogues, but not alkyl analogues have depressant effects on the central nervous system (CNS).
Kimura
T
T
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Watanabe
K
K
Koshigami
M
M
Miyamoto
K
K
Kondo
S
S
Yamamoto
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001380:Azauridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D051379:Mice; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006993:Hypnotics and Sedatives; D001380:Azauridine