Synthesis and Antiviral Evaluation of Phosphoramidate Derivatives of (E)-5-(2-Bromovinyl)-2′-Deoxyuridine-Reference-Cited by-同舟云学术

Synthesis and Antiviral Evaluation of Phosphoramidate Derivatives of (E)-5-(2-Bromovinyl)-2′-Deoxyuridine

Published:2001-10 Issue:5 Volume:12 Page:293-300
ISSN:2040-2066
Container-title:Antiviral Chemistry and Chemotherapy
language:en
Short-container-title:Antivir Chem Chemother

Author:

Harris SA¹,McGuigan C¹,Andrei G²,Snoeck R²,De Clercq E²,Balzarini J²

Affiliation:

1. Welsh School of Pharmacy, Cardiff University, Cardiff, UK

2. Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

Abstract

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 α,α-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.

Publisher

SAGE Publications

Link

http://journals.sagepub.com/doi/pdf/10.1177/095632020101200504

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