Synthesis and evaluation of optically pure dioxolanes as inhibitors of hepatitis C virus RNA replication.
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.
Bera
Sanjib
S
Department of Medicinal Chemistry, Isis Pharmaceuticals, Carlsbad, CA 92008, USA.
Malik
Leila
L
Bhat
Balkrishen
B
Carroll
Steven S
SS
MacCoss
Malcolm
M
Olsen
David B
DB
Tomassini
Joanne E
JE
Eldrup
Anne B
AB
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
D000998:Antiviral Agents; D004148:Dioxolanes; D007202:Indicators and Reagents; D012367:RNA, Viral; D012324:RNA-Dependent RNA Polymerase