Synthesis of N3-substituted uridine and related pyrimidine nucleosides and their antinociceptive effects in mice

Abstract

Seventy eight N3-substituted derivatives of uridine (1), thymidine (2), 2′-deoxyuridine (3), 6-azauridine (4), 2′,3′-O- isopropylideneuridine (5), and arabinofuranosyluracil (6) were synthesized and their antinociceptive effects were evaluated. N3-(2′,4′- Dimethoxyphenacyl)uridine (11), N3-(2′,4′- dimethoxyphenacyl)2′-deoxyuridine (31), and N3-(2′, 5′-dimethoxyphenacyl)arabinofuranosyluracil (6m) possessed 93, 86, and 82% of the antinociceptive effects tested by hot plate, respectively. The antinociceptive effects of three derivatives were 5.8, 5.4, and 5.1-folds of the effect of N3-phenacyluridine (1h) (16%), respectively. The structure-activity relationship of N3-substituted pyrimidine nucleosides was also discussed. © 2005 Pharmaceutical Society of Japan.