Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 76, Issue -, Pages 98-109Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.02.011
Keywords
Flavivirus inhibitors; Dengue virus; Yellow fever virus; Alkylated nucleosides; 3 ',5 '-Di-O-benzhydryl-2 '-deoxyuridine
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Funding
- Erasmus Mundus Cooperation Window
- Hercules Foundation of the Flemish Government [20100225-7]
- EU FP7 project SILVER [HEALTH-F3-2010-260644]
- Marie Curie Initial Training Network EUVIRNA
- Rega Foundation
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Several flaviviruses, such as the yellow fever virus and the dengue virus cause severe and potentially lethal infection in man. Following up on our initial hit 3',5'-bistritylated uridine 1, a series of alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against dengue fever virus and yellow fever virus. Hereto, alkyl and aryl groups were attached at various positions of the sugar ring combined with subtle variation of the heterocyclic base. Among the new series of derivatives, 3',5'-di-O-trityl-5-fluoro-2'-deoxyuridine (39) was the most efficient in this series and inhibited both yellow fever virus and dengue virus replication with a 50% effective concentration (EC50) of similar to 1 mu g/mL without considerable cytotoxicity. The other fluorinated derivatives proved more toxic. Almost all diphenylmethylated pyrimidine nucleosides with 3',5'-di-O-benzhydryl-2'-deoxyuridine (50) as the example were endowed with strong cytotoxic effects down to 1 mu g/mL. (C) 2014 Elsevier Masson SAS. All rights reserved.
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