title: Synthesis and antiviral activity of novel fluorinated 2',3'-dideoxynucleosides.
abstract: A series of 5-(trifluoroethoxymethyl)-2',3'-dideoxyuridines and 5-[bis(trifluoroethoxy)-methyl]-2',3'-dideoxyuridines have been prepared and screened for antiviral activity. The conformations of these compounds are discussed on the bases of NOE studies and the MO calculations. Modelling and NOE studies suggest both syn- and anti conformations for these 5-(2,2,2-trifluoroethoxymethyl)- and 5-[bis(2,2,2-trifluoroethoxy)-methyl]- derivatives. The NOE parameters are also suggested to be more attributable to the nature of the fluorine atom than to structural or conformational changes. Compounds 17, 26 and 30 showed some activity in anti-HIV-1 and anti-HIV-2 assays, but the compounds were devoid of activity against HSV and human rhinovirus. The compounds tested exhibited low cytotoxicity and were inactive against a bank of cancer cells in vitro.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Piyush
authors.initials: P
authors.lastname: Kumar
authors.forename: Kazue
authors.initials: K
authors.lastname: Ohkura
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Seki
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Wiebe
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013601:T-Lymphocytes / Q000821:virology; D014777:Virus Diseases / Q000188:drug therapy*; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D015224:Dideoxynucleosides