title: Novel 5-arylcarbamoyl-2-methylisoxazolidin-3-yl-3-phosphonates as nucleotide analogues.
abstract: A series of 5-substituted 3-phosphonylated isoxazolidines have been obtained via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-heteroaromatic acrylamides. Good trans/cis diastereoselectivities (d.e. 58-76%) of isomeric (3-diethoxyphosphoryl)isoxazolidines were observed. cis- and trans-Isoxazolidine phosphonates were evaluated for their antiviral activity against a broad range of DNA and RNA viruses but were found inactive. Their cytostatic activity toward L1210, CEM, and HeLa cells was also established, and compounds cis-12r and trans-11r having a 2,2-difluorobenzo[d][1,3]dioxole moiety slightly inhibited proliferation of HeLa cells at IC50 values of 186 and 179 μM, respectively.
authors.affiliation: a Bioorganic Chemistry Laboratory, Faculty of Pharmacy , Medical University of Łódź , Łódź , Muszyńskiego , Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kokosza
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Dorota G
authors.initials: DG
authors.lastname: Piotrowska
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D009711:Nucleotides / Q000737:chemistry*; D014780:Viruses / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007555:Isoxazoles; D009711:Nucleotides
keywords: 1,3-dipolar cycloaddition; Modified nucleosides; isoxazolidines; phosphonates