Synthesis and hypnotic activities of 4-thio analogues of N3-substituted uridines.
Reaction of tri-O-acetyluridine (1) with benzyl bromide or 2-chloroacetophenone in the presence of K2CO3 gave the N3-substituted analogues 2a,c. Condensation of 1 with (+/-)-1-phenylethanol or 3,5-dimethylbenzyl alcohol using the Mitsunobu reaction also gave 2b,d in good yields. These compounds were allowed to react with Lawesson's reagent and were subsequently treated with ammonia to afford the 4-thiouracil derivatives 5a-d. Compounds 5a-c showed moderate hypnotic activity in mice. However, N3-(3,5-dimethyl)benzyl derivatives 3d, 5d were found to be almost inactive in this assay.
Kozai
S
S
Institute of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Maruyama
T
T
Kimura
T
T
Yamamoto
I
I
D000818:Animals; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007276:Injections, Intraventricular; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013891:Thiouridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; D013891:Thiouridine; D010424:Pentobarbital