Synthesis of N3-substituted uridine and related pyrimidine nucleosides and their antinociceptive effects in mice.
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.
Shimizu
Tomomi
T
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa, Japan.
Kimura
Toshiyuki
T
Funahashi
Tatsuya
T
Watanabe
Kazuhito
K
Ho
Ing Kang
IK
Yamamoto
Ikuo
I
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D008297:Male; D051379:Mice; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D000700:Analgesics; D011741:Pyrimidine Nucleosides; D014529:Uridine