NOVEL 5-ARYLCARBAMOYL-2-METHYLISOXAZOLIDIN-3-YL-3-PHOSPHONATES AS NUCLEOTIDE ANALOGUES

作者：Kokosza Kamil; Balzarini Jan; Piotrowska Dorota G^*

来源：Nucleosides Nucleotides & Nucleic Acids, 2014, 33(8): 552-582.

DOI：10.1080/15257770.2014.909046

• Modified nucleosides
• phosphonates
• isoxazolidines
• 1,3-dipolar cycloaddition

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 mu M, respectively.

• 出版日期2014
• 单位河北医科大学