title: Nucleosides. 129. Synthesis of antiviral nucleosides: 5-alkenyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracils.
abstract: Synthesis of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracils containing a vinyl (4a), 2-halovinyl (4b-d), or ethyl substituent at C-5 was achieved. These nucleosides were found to be about a log order less active than 2'-fluoro-5-iodo-ara-C (FIAC) against HSV-1, but they are much less cytotoxic against normal human lymphocytes than FIAC. Nucleosides 4a and 4e showed good activity against HSV-1 (ED50 = 0.16 and 0.24 microM, respectively) and HSV-2 (ED50 = 0.69 and 0.65 microM) with very little cytotoxicity (ID50 greater than 100 microM).
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D002460:Cell Line; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007202:Indicators and Reagents; D007668:Kidney; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D018139:Simplexvirus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014529:Uridine / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D007202:Indicators and Reagents; D001086:Arabinofuranosyluracil; D014529:Uridine