Novel 5-Arylcarbamoyl-2-methylisoxazolidin-3-yl-3-phosphonates as Nucleotide Analogues |
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Authors: | Kamil Kokosza Jan Balzarini |
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Affiliation: | 1. Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of ?ód?, ?ód?, Muszyńskiego, Poland;2. Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat, Leuven, Belgium |
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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. |
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Keywords: | Modified nucleosides phosphonates isoxazolidines 1,3-dipolar cycloaddition |
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