title: Synthesis and evaluation of optically pure dioxolanes as inhibitors of hepatitis C virus RNA replication.
abstract: A series of optically pure 1,3-dioxolane nucleoside mimics was synthesized by a synthetic route that allowed incorporation of a 5R-methyl substituent from commercially available starting materials. The pyrrolo[2,3-d]pyrimidine heterocycle was chosen as a substitute for the purine derivative. Coupling of the pyrrolo[2,3-d]pyrimidine and the dioxolane was performed under solid-liquid phase transfer conditions. The ability to inhibit HCV RNA replication was assessed in a cell based subgenomic replicon assay. None of the described compounds displayed significant anti-HCV activity.
authors.affiliation: Department of Medicinal Chemistry, Isis Pharmaceuticals, Carlsbad, CA 92008, USA.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Bera
authors.forename: Leila
authors.initials: L
authors.lastname: Malik
authors.forename: Balkrishen
authors.initials: B
authors.lastname: Bhat
authors.forename: Steven S
authors.initials: SS
authors.lastname: Carroll
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: David B
authors.initials: DB
authors.lastname: Olsen
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Tomassini
authors.forename: Anne B
authors.initials: AB
authors.lastname: Eldrup
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007202:Indicators and Reagents; D008968:Molecular Conformation; D015394:Molecular Structure; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004148:Dioxolanes; D007202:Indicators and Reagents; D012367:RNA, Viral; D012324:RNA-Dependent RNA Polymerase