Chemical & Pharmaceutical Bulletin 2005-03-01

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

Tomomi Shimizu, Toshiyuki Kimura, Tatsuya Funahashi, Kazuhito Watanabe, Ing Kang Ho, Ikuo Yamamoto

Index: Chem. Pharm. Bull. 53 , 313-318, (2005)

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Abstract

Seventy eight N(3)-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. N(3)-(2',4'-Dimethoxyphenacyl)uridine (1l), N(3)-(2',4'-dimethoxyphenacyl)2'-deoxyuridine (3l), and N(3)-(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 N(3)-phenacyluridine (1h) (16%), respectively. The structure-activity relationship of N(3)-substituted pyrimidine nucleosides was also discussed.