title: Evaluation of 2'-α-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase.
abstract: Ribonucleoside phosphonate analogues containing 2'-α-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase. The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1.9-2.1 μM, but only modest cell-based activity in the HCV replicon. Pro-drugs of the parent nucleoside phosphonates improved the cell-based activity.
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. Jay.Parrish@gilead.com
authors: Jay P
authors: JP
authors: Parrish
authors: Sharon K
authors: SK
authors: Lee
authors: Constantine G
authors: CG
authors: Boojamra
authors: Hon
authors: H
authors: Hui
authors: Darius
authors: D
authors: Babusis
authors: Brandon
authors: B
authors: Brown
authors: I-hung
authors: IH
authors: Shih
authors: Joy Y
authors: JY
authors: Feng
authors: Adrian S
authors: AS
authors: Ray
authors: Richard L
authors: RL
authors: Mackman
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005461:Fluorine / Q000737:chemistry*; D016174:Hepacivirus / Q000201:enzymology*; D006801:Humans; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012263:Ribonucleosides / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D012263:Ribonucleosides; D005461:Fluorine; D012321:DNA-Directed RNA Polymerases