Synthesis and antiviral properties of 5-vinylpyrimidine nucleoside analogs

Abstract

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.