Synthesis and antiviral properties of 5-vinylpyrimidine nucleoside analogs.
5-Vinylpyrimidine nucleosides can be readily synthesized via organometallic intermediates from commercially available nucleosides. Highly potent and selective inhibitors of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) are (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and some related analogs such as (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU) and (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC). The selective antiviral action of BVDU is based upon a specific phosphorylation by the virus-encoded deoxythymidine kinase (TK), inhibition of the viral DNA polymerase and/or incorporation into viral DNA. The efficacy of BVDU against HSV-1 and VZV infections has been demonstrated in animal models and phase I clinical trials. Possible limitations in the clinical usefulness of 5-vinylpyrimidine nucleosides in general and BVDU in particular are discussed.
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D005347:Fibroblasts; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D051379:Mice; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides; C020235:brivudine; D001973:Bromodeoxyuridine