Sedative and hypnotic activities of pyrimidine nucleoside derivatives.

N3-Substituted pyrimidine nucleoside and their related compounds were synthesized. The central nervous system (CNS) depressant effect of the compounds such as hypnotic activity and synergistic effect with pentobarbital have been evaluated. N3-Phenacyl derivatives of uridine (2), thymidine (3), deoxyuridine (4), 6-azauridine (5) and arabinofuranosyluracil (6) exhibited the hypnotic activity, whereas N3-phenacyl-2',3'-O-isopropylideneuridine did not. Compound 2, 3, 4 and 6 significantly enhanced pentobarbital-induced sleep. The results indicate that CNS depressant effect of pyrimidine nucleoside derivatives might relate to functional group at the N3-position on oxopyrimidine ring and stereospecificity of sugar moiety at the N1-position.