Kokosza Kamil, Balzarini Jan, Piotrowska Dorota G
a Bioorganic Chemistry Laboratory, Faculty of Pharmacy , Medical University of Łódź , Łódź , Muszyńskiego , Poland.
Nucleosides Nucleotides Nucleic Acids. 2014;33(8):552-82. doi: 10.1080/15257770.2014.909046.
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.
通过N-甲基-C-（二乙氧基磷酰基）硝酮与N-杂芳基丙烯酰胺的环加成反应，得到了一系列5-取代的3-膦酰化异恶唑烷。观察到异构（3-二乙氧基磷酰基）异恶唑烷具有良好的反式/顺式非对映选择性（d.e. 58-76%）。对顺式和反式异恶唑烷膦酸酯针对多种DNA和RNA病毒的抗病毒活性进行了评估，但发现其无活性。还确定了它们对L1210、CEM和HeLa细胞的细胞生长抑制活性，具有2,2-二氟苯并[d][1,3]二氧戊环部分的化合物顺式-12r和反式-11r分别在IC50值为186和179 μM时对HeLa细胞的增殖有轻微抑制作用。
