期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 19, 期 15, 页码 4445-4453出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2011.06.045
关键词
Acyclic nucleoside phosphonates; Drug design; Antiviral activity; Purines; Pyrimidines
资金
- Institute of Organic Chemistry and Biochemistry [AVOZ40550506]
- Agency of the Czech Republic [P207/11/0108]
- Centre for New Antivirals and Antineoplastics (Ministry of Education, Youth and Sports of the Czech Republic) [1M0508]
- Gilead Sciences, Inc. (Foster City, CA, USA)
- Geconcerteerde Onderzoeksacties (GOA) of the KU Leuven [10/014]
Series of novel acyclic nucleoside phosphonates (ANPs) with various nucleobases and 2-(2-phosphonoethoxy) ethyl (PEE) chain bearing various substituents in beta-position to the phosphonate moiety were prepared. The influence of structural alternations on antiviral activity was studied. Several derivatives exhibit antiviral activity against HIV and vaccinia virus (middle micromolar range), HSV-1 and HSV-2 (lower micromolar range) and VZV and CMV (nanomolar range), although the parent unbranched PEE-ANPs are inactive. Adenine as a nucleobase and the methyl group attached to the PEE chain proved to be a prerequisite to afford pronounced antiviral activity. (C) 2011 Elsevier Ltd. All rights reserved.
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