title: The application of phosphoramidate ProTide technology to the potent anti-HCV compound 4'-azidocytidine (R1479).
abstract: We report the design, synthesis and evaluation of a family of ca 50 phosphoramidate ProTides of the potent anti-HCV compound 4'-azidocytidine (R1479), with variation on the ester, amino acid and aryl moiety of the ProTide. Sub-muM inhibitors of HCV emerge. The compounds are all non-cytotoxic in the replicon assay. We herein report detailed SARs for each of the regions of the ProTide.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK. mcguigan@cardiff.ac.uk
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
authors.forename: Mary Rose
authors.initials: MR
authors.lastname: Kelleher
authors.forename: Plinio
authors.initials: P
authors.lastname: Perrone
authors.forename: Sinead
authors.initials: S
authors.lastname: Mulready
authors.forename: Giovanna
authors.initials: G
authors.lastname: Luoni
authors.forename: Felice
authors.initials: F
authors.lastname: Daverio
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: Joseph A
authors.initials: JA
authors.lastname: Martin
authors.forename: Klaus
authors.initials: K
authors.lastname: Klumpp
authors.forename: David B
authors.initials: DB
authors.lastname: Smith
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008956:Models, Chemical; D011355:Prodrugs; D012093:Replicon / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods*; D014779:Virus Replication
chemical_list: D000596:Amino Acids; D000998:Antiviral Agents; D011355:Prodrugs; D003562:Cytidine; C508950:4'-azidocytidine