title: Synthesis and characterization of 2'-C-Me branched C-nucleosides as HCV polymerase inhibitors.
abstract: A series of 2'-C-methyl branched purine and pyrimidine C-nucleosides were prepared. Their anti-HCV activity and pharmacological properties were profiled, and compared with known 2'-C-Me N-nucleoside counterparts. In particular, 2'-C-Me 4-aza-7,9-dideazaadenosine C-nucleoside (2) was found to have potent and selective anti-HCV activity in vitro as well as a favorable pharmacokinetic profile and in vivo potential for enhanced potency over the corresponding N-nucleoside.
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94044, USA. acho@gilead.com
authors.forename: Aesop
authors.initials: A
authors.lastname: Cho
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Darius
authors.initials: D
authors.lastname: Babusis
authors.forename: Thomas
authors.initials: T
authors.lastname: Butler
authors.forename: Rick
authors.initials: R
authors.lastname: Lee
authors.forename: Oliver L
authors.initials: OL
authors.lastname: Saunders
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Jay
authors.initials: J
authors.lastname: Parrish
authors.forename: Jason
authors.initials: J
authors.lastname: Perry
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Feng
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Ray
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D004285:Dogs; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D007275:Injections, Intravenous; D061251:Primary Cell Culture; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D001372:Aza Compounds; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase