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

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

  • ACS Med Chem Lett. 2020 Jun 24;11(7):1410-1415. doi: 10.1021/acsmedchemlett.0c00090.
Min Luo 1,  Elisabetta Groaz 1,  Robert Snoeck 2,  Graciela Andrei 2,  Piet Herdewijn 1
Affiliations

Affiliations

  • 1 Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49 box 1041, 3000 Leuven, Belgium.
  • 2 Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Herestraat 49 box 1043, 3000 Leuven, Belgium.
PMID: 32676147 DOI: 10.1021/acsmedchemlett.0c00090
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.

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