title: The design, synthesis, and antiviral activity of 4'-azidocytidine analogues against hepatitis C virus replication: the discovery of 4'-azidoarabinocytidine.
abstract: 4'-Azidocytidine 3 (R1479) has been previously discovered as a potent and selective inhibitor of HCV replication targeting the RNA-dependent RNA polymerase of hepatitis C virus, NS5B. Here we describe the synthesis and biological evaluation of several derivatives of 4'-azidocytidine by varying the substituents at the ribose 2' and 3'-positions. The most potent compound in this series is 4'-azidoarabinocytidine with an IC(50) of 0.17 microM in the genotype 1b subgenomic replicon system. The structure-activity relationships within this series of nucleoside analogues are discussed.
authors.affiliation: Roche Palo Alto LLC, Palo Alto, California 94304, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Smith
authors.forename: Genadiy
authors.initials: G
authors.lastname: Kalayanov
authors.forename: Christian
authors.initials: C
authors.lastname: Sund
authors.forename: Anna
authors.initials: A
authors.lastname: Winqvist
authors.forename: Pedro
authors.initials: P
authors.lastname: Pinho
authors.forename: Tatiana
authors.initials: T
authors.lastname: Maltseva
authors.forename: Veronique
authors.initials: V
authors.lastname: Morisson
authors.forename: Vincent
authors.initials: V
authors.lastname: Leveque
authors.forename: Sonal
authors.initials: S
authors.lastname: Rajyaguru
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Pogam
authors.forename: Isabel
authors.initials: I
authors.lastname: Najera
authors.forename: Kurt
authors.initials: K
authors.lastname: Benkestock
authors.forename: Xiao-Xiong
authors.initials: XX
authors.lastname: Zhou
authors.forename: Hans
authors.initials: H
authors.lastname: Maag
authors.forename: Nick
authors.initials: N
authors.lastname: Cammack
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martin
authors.forename: Steven
authors.initials: S
authors.lastname: Swallow
authors.forename: Nils Gunnar
authors.initials: NG
authors.lastname: Johansson
authors.forename: Klaus
authors.initials: K
authors.lastname: Klumpp
authors.forename: Mark
authors.initials: M
authors.lastname: Smith
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C534614:4'-azidoarabinocytidine; D000998:Antiviral Agents; D003561:Cytarabine