Prodrugs of Nucleoside 5'-Monophosphate Analogues: Overview of
the Recent Literature Concerning their Synthesis and Applications

Béatrice      Roy; Valentin      Navarro; Suzanne      Peyrottes
doi:10.2174/0929867329666220909122820
Abstract

Nucleoside analogues are widely used as anti-infectious and antitumoral agents. However, their clinical use may face limitations associated with their physicochemical properties, pharmacokinetic parameters, and/or their peculiar mechanisms of action. Indeed, once inside the cells, nucleoside analogues require to be metabolized into their corresponding (poly-)phosphorylated derivatives, mediated by cellular and/or viral kinases, in order to interfere with nucleic acid biosynthesis. Within this activation process, the first-phosphorylation step is often the limiting one and to overcome this limitation, numerous prodrug approaches have been proposed. Herein, we will focus on recent literature data (from 2015 and onwards) related to new prodrug strategies, the development of original synthetic approaches and novel applications of nucleotide prodrugs (namely pronucleotides) leading to the intracellular delivery of 5’-monophosphate nucleoside analogues.
Keywords: Pronucleotide, Phosphotriester, Phosphodiester, Phosphoramidate, Phosphorodiamidate, Asymmetric Synthesis, Chemotherapy.
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DOI https://dx.doi.org/10.2174/0929867329666220909122820	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Prodrugs of Nucleoside 5'-Monophosphate Analogues: Overview of the Recent Literature Concerning their Synthesis and Applications

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