title: Design, synthesis, antiviral and cytostatic evaluation of novel isoxazolidine nucleotide analogues with a 1,2,3-triazole linker.
abstract: Azidation (TMSN(3), SnCl(4)) of a 9:1 mixture of trans- and cis-5-acetoxy-2-methylisoxazolidin-3-yl-3-phosphonates at the anomeric carbon atom led to the formation of the equimolar mixture of cis- and trans-5-azido-2-methylisoxazolidin-3-yl-3-phosphonates, which were efficiently separated. The 1,3-dipolar cycloaddition of pure trans- and cis-5-azidoisoxazolidin-3-yl-3-phosphonates with selected alkynes gave the respective nucleoside mimetics containing a 1,2,3-triazole linker. The (1,2,3-triazolyl)isoxazolidine phosphonates obtained herein were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. Compounds 15f-j and 16f-j were cytostatic in the higher micromolar range.
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, 90-151 Łódź, Muszyńskiego 1, Poland. dorota.piotrowska@umed.lodz.pl
authors.forename: Dorota G
authors.initials: DG
authors.lastname: Piotrowska
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Iwona E
authors.initials: IE
authors.lastname: Głowacka
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D014230:Triazoles / Q000737:chemistry*; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D054697:Cytostatic Agents; D009711:Nucleotides; D014230:Triazoles