Synthesis and central nervous system depressant effects of N3-substituted 2',3'-O-isopropylideneuridines.
N3-Substituted derivatives of 2',3'-O-isopropylideneuridine (1) were synthesized and their pharmacological effects on the central nervous system (CNS) examined using mice. Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyls (8, 9, 10), and alpha-phenylethyl (11) derivatives of 1 were administered to mice by intracerebroventricular (i.c.v.) injection for evaluating hypnotic activity, pentobarbital-induced sleep prolongation, and spontaneous activity as indices. Only 3 possessed hypnotic activity by i.c.v. injection at the dose of 2.0 mumol/mouse. Compounds 3, 4, and 10 significantly showed synergism with a barbiturate, indicating that the derivatives have some CNS depressant effects. Moreover, 3 and 4 caused decrease in the spontaneous activity of mice, even at low doses. The present study indicated that substitution by ethyl, propyl, and p-xylyl groups at the N3-position of 2',3'-O-isopropylideneuridine imparted the CNS depressant effects.
Yao
C S
CS
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Kimura
T
T
Watanabe
K
K
Kondo
S
S
Ho
I K
IK
Yamamoto
I
I
D000818:Animals; D002492:Central Nervous System Depressants / Q000138:chemical synthesis* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D009705:Nucleosides; D010424:Pentobarbital