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Amidate Prodrugs of O-2-Alkylated Pyrimidine Acyclic Nucleosides Display Potent Anti-Herpesvirus Activity.

ABSTRACT: Three series of amidate prodrugs of O-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 (R)-O-2-alkylated FPMPC exhibited potent anti-HCMV and VZV activity in the micromolar range. In addition, the valine ester prodrugs of 5-fluorocytosine (R)-O-2-alkylated FPMP and (R)-O-2-alkylated cHPMPC showed inhibitory activity at molar concentrations against these viruses.

SUBMITTER: Luo M

PROVIDER: S-EPMC7359042 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Amidate Prodrugs of O-2-Alkylated Pyrimidine Acyclic Nucleosides Display Potent Anti-Herpesvirus Activity.

Luo Min M Groaz Elisabetta E Snoeck Robert R Andrei Graciela G Herdewijn Piet P

ACS medicinal chemistry letters 20200624 7

Three series of amidate prodrugs of O-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 (R)-O-2-alkylated FPMPC exhibited potent anti-HCMV and VZV activity in the micromolar range. In addition, the valine ester p ...[more]

PMID: 32676147

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