膦酰化二氢异恶唑核苷的合成与生物学评价

Synthesis and biological evaluation of phosphonated dihydroisoxazole nucleosides.

作者信息

Romeo Giovanni, Iannazzo Daniela, Piperno Anna, Romeo Roberto, Saglimbeni Monica, Chiacchio Maria Assunta, Balestrieri Emanuela, Macchi Beatrice, Mastino Antonio

机构信息

Dipartimento Farmaco-Chimico, Università di Messina, Via SS. Annunziata, Messina 98168, Italy.

出版信息

Bioorg Med Chem. 2006 Jun 1;14(11):3818-24. doi: 10.1016/j.bmc.2006.01.028. Epub 2006 Feb 15.

DOI:10.1016/j.bmc.2006.01.028

PMID:16480883

Abstract

Phosphonated isoxazolinyl nucleosides have been prepared via 1,3-dipolar cycloaddition reaction of nitrile oxides with corresponding vinyl or allyl nucleobases for antiviral studies. The cytotoxicity, the anti-HSV activity and the RT-inhibitory activity of the obtained compounds were evaluated and compared with those of AZT and diethyl{(1'SR,4'RS)-1'-[[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)]-3'-methyl-2'-oxa-3'-azacyclopent-4'-yl]}methylphosphonate, a saturated phosphonated dihydroisoxazole nucleoside analogue.

摘要

为了进行抗病毒研究，通过腈氧化物与相应的乙烯基或烯丙基核苷酸碱基的1,3-偶极环加成反应制备了膦酸化异恶唑啉基核苷。评估了所得化合物的细胞毒性、抗单纯疱疹病毒（HSV）活性和逆转录酶（RT）抑制活性，并与齐多夫定（AZT）以及饱和膦酸化二氢异恶唑核苷类似物二乙基{（1'SR,4'RS）-1'-[[（5-甲基-2,4-二氧代-3,4-二氢嘧啶-1（2H）-基）]-3'-甲基-2'-氧杂-3'-氮杂环戊-4'-基]}甲基膦酸酯的活性进行了比较。