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Synthesis 2009(5): 841-847  
DOI: 10.1055/s-0028-1083369
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of New Cyclic and Acyclic 5-Halouridine Derivatives as Potential Antiviral Agents

Mohamed F. Elshehrya,b, Jan Balzarinic, Chris Meier*a
a Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
Fax: +49(40)428385592; e-Mail: chris.meier@chemie.uni-hamburg.de;
b Pesticides Department, National Research Centre, 12622 Dokki, Cairo, Egypt
c Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium
Further Information

Publication History

Received 4 September 2008
Publication Date:
11 February 2009 (online)

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Abstract

The synthesis of new cyclic and acyclic nucleoside analogues was achieved by alkylation of 5-halogenated 6-(2,4-dichlorophenoxymethyl)pyrimidine-2,4-dione following the Vorbrüggen coupling procedure. Nucleoside analogues of the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)-type were obtained as well as analogues of ganciclovir, acyclovir, and ribonucleosides. All compounds were tested against a variety of viruses. Three of the new compounds were potent and selective anti-HIV-1 inhibitors.

Key words

bioorganic chemistry - drugs - antiviral agents - nucleosides - glycosylation

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All new compounds were evaluated concerning their ability to inhibit the replication of HIV in T-lymphocytes cells. Briefly, a CEM cell suspension was infected with HIV-1 or HIV-2. The mutant thymidine kinase-deficient CEM cell cultures were only infected with HIV-2. Then, 100 µL of the infected cell suspensions was transferred into 96-well microtiter plate wells and mixed with 100 µL of the appropriate dilutions of the test compounds. After 4-5 days, giant cell formation was recorded microscopically in the HIV-infected cell cultures.