title: Synthesis and characterization of 1'-C-cyano-2'-fluoro-2'-C-methyl pyrimidine nucleosides as HCV polymerase inhibitors.
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.
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Thorsten A
authors: TA
authors: Kirschberg
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Michael R
authors: MR
authors: Mish
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Lijun
authors: L
authors: Zhang
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Neil H
authors: NH
authors: Squires
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Ke-Yu
authors: KY
authors: Wang
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Aesop
authors: A
authors: Cho
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Joy Y
authors: JY
authors: Feng
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Martijn
authors: M
authors: Fenaux
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Darius
authors: D
authors: Babusis
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Yeojin
authors: Y
authors: Park
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Adrian S
authors: AS
authors: Ray
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors: Choung U
authors: CU
authors: Kim
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D054879:Halogenation; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008745:Methylation; D010756:Phosphoric Acids / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D012093:Replicon / Q000187:drug effects
chemical_list: D000577:Amides; D000998:Antiviral Agents; D010756:Phosphoric Acids; D011355:Prodrugs; D011741:Pyrimidine Nucleosides; C011067:phosphoramidic acid; D012324:RNA-Dependent RNA Polymerase
keywords: HCV antivirals; Nucleotide phosphoramidate prodrugs; Pyrimidine nucleoside analogs