Synthesis and characterization of 1'-C-cyano-2'-fluoro-2'-C-methyl pyrimidine nucleosides as HCV polymerase inhibitors

  • Bioorg Med Chem Lett. 2015 Mar 1;25(5):1040-3. doi: 10.1016/j.bmcl.2015.01.021.
Thorsten A Kirschberg  1 ,  Michael R Mish  1 ,  Lijun Zhang  1 ,  Neil H Squires  1 ,  Ke-Yu Wang  1 ,  Aesop Cho  1 ,  Joy Y Feng  1 ,  Martijn Fenaux  1 ,  Darius Babusis  1 ,  Yeojin Park  1 ,  Adrian S Ray  1 ,  Choung U Kim  1
Affiliations
  • 1. Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
PMID: 25650256 DOI: 10.1016/j.bmcl.2015.01.021
Abstract

The first synthesis of 1'-C-CN, 2'-F, 2'-C-Me pyrimidines is described. Anti-HCV activity was assessed and compared to the 1'-C-CN, 2'-C-Me as well as the 2'-F, 2'-C-Me pyrimidines. A phosphoramidate prodrug of the cytidine derivative showed activity in the low micromolar range against HCV replicons.

Keywords
HCV antivirals; Nucleotide phosphoramidate prodrugs; Pyrimidine nucleoside analogs.