title: Discovery of 4'-azido-2'-deoxy-2'-C-methyl cytidine and prodrugs thereof: a potent inhibitor of Hepatitis C virus replication.
abstract: 4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC(50) value of 1.2 μM and showing moderate in vivo bioavailability in rat (F=14%). Here we describe the synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and prodrug derivatives thereof.
authors.affiliation: Medivir AB, PO Box 1086, SE-141 22 Huddinge, Sweden. magnus.k.nilsson@telia.com
authors.forename: Magnus
authors.initials: M
authors.lastname: Nilsson
authors.forename: Genadiy
authors.initials: G
authors.lastname: Kalayanov
authors.forename: Anna
authors.initials: A
authors.lastname: Winqvist
authors.forename: Pedro
authors.initials: P
authors.lastname: Pinho
authors.forename: Christian
authors.initials: C
authors.lastname: Sund
authors.forename: Xiao-Xiong
authors.initials: XX
authors.lastname: Zhou
authors.forename: Horst
authors.initials: H
authors.lastname: Wähling
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Belfrage
authors.forename: Michael
authors.initials: M
authors.lastname: Pelcman
authors.forename: Tatiana
authors.initials: T
authors.lastname: Agback
authors.forename: Kurt
authors.initials: K
authors.lastname: Benckestock
authors.forename: Kristina
authors.initials: K
authors.lastname: Wikström
authors.forename: Mirva
authors.initials: M
authors.lastname: Boothee
authors.forename: Anneli
authors.initials: A
authors.lastname: Lindqvist
authors.forename: Christina
authors.initials: C
authors.lastname: Rydegård
authors.forename: Tim H M
authors.initials: TH
authors.lastname: Jonckers
authors.forename: Koen
authors.initials: K
authors.lastname: Vandyck
authors.forename: Pierre
authors.initials: P
authors.lastname: Raboisson
authors.forename: Tse-I
authors.initials: TI
authors.lastname: Lin
authors.forename: Sophie
authors.initials: S
authors.lastname: Lachau-Durand
authors.forename: Herman
authors.initials: H
authors.lastname: de Kock
authors.forename: David B
authors.initials: DB
authors.lastname: Smith
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martin
authors.forename: Klaus
authors.initials: K
authors.lastname: Klumpp
authors.forename: Kenneth
authors.initials: K
authors.lastname: Simmen
authors.forename: Lotta
authors.initials: L
authors.lastname: Vrang
authors.forename: Ylva
authors.initials: Y
authors.lastname: Terelius
authors.forename: Bertil
authors.initials: B
authors.lastname: Samuelsson
authors.forename: Sa
authors.initials: S
authors.lastname: Rosenquist
authors.forename: Nils Gunnar
authors.initials: NG
authors.lastname: Johansson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D055808:Drug Discovery; D016174:Hepacivirus / Q000187:drug effects*; D011355:Prodrugs / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D051381:Rats; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011355:Prodrugs; D017361:Viral Nonstructural Proteins; D003841:Deoxycytidine; D003562:Cytidine; C578070:4'-azido-2'-deoxy-2'-methylcytidine; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase