Acyclic nucleoside analogues bearing phosphonomethoxy residues in the side chain (ANP) attract much attention due to a very beneficial combination of biological properties. Intensive work of organic chemists during the last two decades resulted in a large panel of new compounds that were evaluated as potential antiviral drugs. Herein, we present an overview of major chemical structures within the group of acyclic nucleoside analogues containing phosphonomethoxy side fragments and describe main aspects of their synthesis and antiviral potential. We also describe progress in "prodrug" approaches applied to this chemical group to improve pharmacokinetic profiles of the potential candidates. Chemical modifications in the molecule of parental ANP aimed at blocking of phosphonate charges resulted in a set of promising derivatives, two of which have been recently approved for treatment of hepatits B (Hepsera®) and HIV (Viread®). The preparation, antiviral properties and some aspects of metabolic transformations and pharmacokinetics of ANP prodrugs are discussed.
Keywords: Acyclic nucleoside analogues, phosphonomethoxy groups, prodrugs, antiviral properties
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