5-O-Alkylated derivatives of 5-hydroxy-2'-deoxyuridine as potential antiviral agents. Anti-herpes activity of 5-propynyloxy-2'-deoxyuridine.
Alkylation of 5-hydroxyuridine or 5-hydroxy-2'-deoxyuridine with various activated alkylating agents in the presence of 1 equiv of NaOH gave a series of new nucleoside analogues which were evaluated for antiviral activity against vaccinia virus, herpes simplex-1 virus, and vesicular stomatitis virus in both primary rabbit kidney cells and human skin fibroblasts. One of these analogues, 5-propynyloxy-2'-deoxyuridine, was a potent inhibitor of herpes simplex virus. Structure-activity considerations suggest that the anti-herpes activity is dependent on the integrity of the acetylene group since substitution of phenyl, p-nitrophenyl, vinyl, carboxamido, or carboxyl for the triple bond led to diminished antiviral activity.
D000998:Antiviral Agents / Q000138:chemical synthesis*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014616:Vaccinia virus / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000998:Antiviral Agents; C016081:propynyloxy-2'-deoxyuridine; D003857:Deoxyuridine