title: Design, synthesis and biological evaluation of 2'-deoxy-2',2'-difluoro-5-halouridine phosphoramidate ProTides.
abstract: We report the synthesis of a series of novel 2'-deoxy-2',2'-difluoro-5-halouridines and their corresponding phosphoramidate ProTides. All compounds were evaluated for antiviral activity and for cellular toxicity. Interestingly, 2'-deoxy-2',2'-difluoro-5-iodo- and -5-bromo-uridines showed selective activity against feline herpes virus replication in cell culture due to a specific recognition (activation) by the virus-encoded thymidine kinase.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Quintiliani
authors.forename: Leentje
authors.initials: L
authors.lastname: Persoons
authors.forename: Nicola
authors.initials: N
authors.lastname: Solaroli
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D010756:Phosphoric Acids; D005467:Floxuridine; C011067:phosphoramidic acid