title: Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides.
abstract: A series of 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4'-azanucleosides were prepared as a separable mixture of α- and β-anomers. The 6-chloropurine analogue was obtained as a mixture of N(7) and N(9) regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4'-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC(50)=36.9μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity.
authors.affiliation: Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, Oviedo (Asturias), Spain.
authors.forename: Saúl
authors.initials: S
authors.lastname: Martínez-Montero
authors.forename: Susana
authors.initials: S
authors.lastname: Fernández
authors.forename: Yogesh S
authors.initials: YS
authors.lastname: Sanghvi
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Theodorakis
authors.forename: Mervi A
authors.initials: MA
authors.lastname: Detorio
authors.forename: Tamara R
authors.initials: TR
authors.lastname: McBrayer
authors.forename: Tony
authors.initials: T
authors.lastname: Whitaker
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.forename: Vicente
authors.initials: V
authors.lastname: Gotor
authors.forename: Miguel
authors.initials: M
authors.lastname: Ferrero
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D054879:Halogenation; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000998:Antiviral Agents; D001372:Aza Compounds; D009705:Nucleosides