Synthesis and antiviral evaluation of phosphoramidate derivatives of (E)-5-(2-bromovinyl)2′-deoxyuridine

被引：18

作者：

Harris, SA

McGuigan, C ^{[1
]}

Andrei, G

Snoeck, R

De Clercq, E

Balzarini, J

机构：

[1] Cardiff Univ, Welsh Sch Pharm, Cardiff, S Glam, Wales

[2] Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium

来源：

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY | 2001年 / 12卷 / 05期

关键词：

antiherpetic nucleoside analogues; (E)-5-(2-bromovinyl)-2 '-deoxyuridine (BVDU); phosphoramidates; kinase-bypass;

D O I：

10.1177/095632020101200504

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report the design, synthesis and antiviral evaluation of a number of lipophilic, masked phosphoramidate derivatives of the antiherpetic agent (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), designed to act as membrane soluble prodrugs of the free nucleotide. The phosphoramidate derivatives of BVDU that contain L-alanine exhibited potent anti herpes simplex virus type 1 and varicella-zoster virus activity but lost marked activity against thymidine kinase-deficient virus strains. The phosphoramidate derivative bearing the amino acid alpha,alpha-dimethylglycine showed poor activity in all cell lines tested. It appears that successful kinase bypass by phosphoramidates is highly dependent on the nucleoside analogue, amino acid and ester structure, as well as the cell line to which the drugs are exposed.

引用

页码：293 / 300

页数：8

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