Hypnotic action of N3-substituted arabinofuranosyluracils on mice.
Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyl (8-10), and alpha-phenylethyl (11) derivatives of arabinofuranosyluracil (1) were synthesized and their pharmacological effects in mice were examined by using hypnotic activity and synergism with pentobarbital as indices for the CNS depressant effects. At a dose of 2.0 micromol/mouse by intracerebroventricular injection, the values of mean sleeping time induced by 7-11 were 144, 154, 117, 33, and 34 min, respectively, whereas the alkyl (2-6) derivatives did not cause any hypnotic activity. N3-o-Xylylarabinofuranosyluracil (8) displayed the most potent hypnotic activity among the derivatives tested. Certain derivatives (6-11) significantly prolonged the pentobarbital-induced sleeping time compared to control. The present study indicated that substitution with benzyl and/or related groups on the N3-position of arabinofuranosyluracil produced CNS depressant effects.
Kimura
T
T
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Yao
S
S
Watanabe
K
K
Kondo
S
S
Ho
I K
IK
Yamamoto
I
I
D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship
D006993:Hypnotics and Sedatives; D001086:Arabinofuranosyluracil