title: Synthesis and antiviral activity of monofluoro and difluoro analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1).
abstract: A range of 2'-fluoro and 2',3'-difluoro analogues of pyrimidine deoxyribonucleosides have been synthesized and evaluated against human immunodeficiency virus (HIV-1) in a human lymphoblastoid cell line. Among these compounds, 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12), 2',3'-didehydro-2',3'-dideoxy-2'-fluorocytidine (35), 1-(2,3-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)cytosine (41), and 3'-deoxy-2',3'-didehydro-2'-fluorothymidine (45) were found to have significant antiviral activity, with IC50 values of 0.65, 10, 10, and 100 microM, respectively. The structure-activity relationships are discussed.
authors.affiliation: Research Division, Roche Products Limited, Welwyn Garden City, Hertfordshire, England.
authors.forename: J A
authors.initials: JA
authors.lastname: Martin
authors.forename: D J
authors.initials: DJ
authors.lastname: Bushnell
authors.forename: I B
authors.initials: IB
authors.lastname: Duncan
authors.forename: S J
authors.initials: SJ
authors.lastname: Dunsdon
authors.forename: M J
authors.initials: MJ
authors.lastname: Hall
authors.forename: P J
authors.initials: PJ
authors.lastname: Machin
authors.forename: J H
authors.initials: JH
authors.lastname: Merrett
authors.forename: K E
authors.initials: KE
authors.lastname: Parkes
authors.forename: N A
authors.initials: NA
authors.lastname: Roberts
authors.forename: G J
authors.initials: GJ
authors.lastname: Thomas
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003853:Deoxyribonucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000494:pharmacology; D005461:Fluorine; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D015394:Molecular Structure; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D016047:Zalcitabine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D003853:Deoxyribonucleosides; D015224:Dideoxynucleosides; D011741:Pyrimidine Nucleosides; C065050:1-(2,3-dideoxy-2-fluoropentofuranosyl)cytosine; C065051:2',3'-dideoxy-2',3'-didehydro-2'-fluorocytidine; C065053:3'-deoxy-2',3'-didehydro-2'fluorothymidine; C065052:1-(2,3-dideoxy-2,3-difluoroarabinofuranosyl)cytosine; D005461:Fluorine; D016047:Zalcitabine