Three series of amidate prodrugs of -2-alkylated acyclic nucleosides of the 3-fluoro-2-(phosphonomethoxy)propyl (FPMP), cyclic 3-hydroxy-2-(phosphonomethoxypropyl) (cHPMP), and 2-(phosphonomethoxypropyl) (PMP)-type featuring cytosine and 5-fluorocytosine as nucleobases were readily synthesized. Both the aspartic acid ester and valine ester prodrugs of ()--2-alkylated FPMPC exhibited potent anti-HCMV and VZV activity in the micromolar range. In addition, the valine ester prodrugs of 5-fluorocytosine ()--2-alkylated FPMP and ()--2-alkylated cHPMPC showed inhibitory activity at molar concentrations against these viruses.
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| http://dx.doi.org/10.1021/acsmedchemlett.0c00090 | DOI Listing |
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