title: Synthesis and anti-HIV activity of thymidine analogues bearing a 4'-cyanovinyl group and some derivatives thereof.
abstract: Treatment of 3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine (4) with potassium or magnesium nitromethanide afforded in good yield the resolvable epimeric mixture of the expected blocked nitronucleosides 5 which upon dehydration led to the corresponding E-nitroenofuranosylthymidine 6. Nucleophilic attack of cyanide onto the nitrovinyl group led to a nucleoside analogue bearing a terminal 1-cyanovinyl group (7), a soft electrophilic group which, upon reaction with benzeneselenol, underwent a conjugate addition to the phenylselenonucleoside derivative 9. All these compounds, eventually de-O-silylated, were subject of in vitro biological testing, some exhibiting interesting cytotoxic or antiviral properties.
authors.affiliation: Department of Organic Pharmaceutical Chemistry, University of Geneva, Sciences II, Switzerland.
authors.forename: J M
authors.initials: JM
authors.lastname: Tronchet
authors.forename: I
authors.initials: I
authors.lastname: Kovacs
authors.forename: P
authors.initials: P
authors.lastname: Dilda
authors.forename: M
authors.initials: M
authors.lastname: Seman
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D012821:Silanes / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C458779:3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine; D019380:Anti-HIV Agents; D012821:Silanes; D013936:Thymidine