title: Preparation and biological evaluation of 1'-cyano-2'-C-methyl pyrimidine nucleosides as HCV NS5B polymerase inhibitors.
abstract: The first synthesis of 1'-cyano-2'-C-methyl pyrimidine nucleosides is described. Anti-HCV activity of these nucleosides and their nucleotide phosphoramidate prodrugs was assessed and compared to the 1'-unsubstituted counterparts and to the related 1'-cyano-2'-C-methyl C-nucleoside parent of GS-6620.
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA. Electronic address: mmish@gilead.com.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mish
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Aesop
authors.initials: A
authors.lastname: Cho
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kirschberg
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: C Sebastian
authors.initials: CS
authors.lastname: Zonte
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Martijn
authors.initials: M
authors.lastname: Fenaux
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Yeojin
authors.initials: Y
authors.lastname: Park
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Darius
authors.initials: D
authors.lastname: Babusis
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Feng
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Ray
authors.affiliation: Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94044, USA.
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009705:Nucleosides; D011741:Pyrimidine Nucleosides; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCV antivirals; NS5B polymerase inhibitor; Nucleotide phosphoramidate prodrugs; Pyrimidine nucleoside analogs