硼膦酸盐 AZT 和 d4T 单磷酸酯的同系物的合成及抗病毒活性。

Synthesis and antiviral activity of boranophosphonate isosteres of AZT and d4T monophosphates.

机构信息

Laboratoire d'Architecture et Fonction des Macromolécules Biologiques, UMR CNRS 6098, Equipe Réplicases Virales, Structure, Mécanisme, et Drug-design, Universités Aix-Marseille I et II, Parc scientifique de Luminy, 163 av de Luminy, Case 932, 13288 Marseille Cedex 9, France.

出版信息

Eur J Med Chem. 2010 Feb;45(2):849-56. doi: 10.1016/j.ejmech.2009.11.012. Epub 2009 Nov 12.

DOI:10.1016/j.ejmech.2009.11.012

PMID:19969396

Abstract

We report synthesis, in vitro antiviral activity, and stability studies in biological media of original boranophosphonate isosteres of AZT and d4T monophophates. A convenient route for the synthesis of 3'-Azido-3'-deoxythymidine-5'-boranophosphonate 8 and 2',3'-Didehydro-3'-dideoxythymidine-5'-boranophosphonate 12 is described. H-phosphinates 7 and 11, and alpha-boranophosphonates 8 and 12 exhibited no significant in vitro activity against HIV-infected cells, neither against a broad panel of viruses, up to 200 microM. The absence of activity of target compounds 8 and 12 can be partially explained by their short half-life in culture medium.

摘要

我们报告了 AZT 和 d4T 单磷酸盐的硼膦酸盐等排物的合成、体外抗病毒活性和在生物介质中的稳定性研究。描述了 3'-叠氮基-3'-去氧胸苷-5'-硼膦酸盐 8 和 2',3'-二氢-3'-去氧胸苷-5'-硼膦酸盐 12 的方便合成路线。H-膦酸酯 7 和 11 以及 α-硼膦酸盐 8 和 12 对感染 HIV 的细胞以及高达 200 μM 的广泛病毒均无明显的体外活性。靶化合物 8 和 12 的活性缺失可以部分解释为它们在培养基中的半衰期较短。