Synthesis and antiviral evaluation of cyclopentyl nucleoside phosphonates

  • Eur J Med Chem. 2018 Apr 25:150:616-625. doi: 10.1016/j.ejmech.2018.03.008.
Mengmeng Wang  1 ,  Puneet Srivastava  1 ,  Chao Liu  1 ,  Robert Snoeck  2 ,  Graciela Andrei  2 ,  Steven De Jonghe  2 ,  Piet Herdewijn  3
Affiliations
  • 1. Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
  • 2. Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
  • 3. Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. Electronic address: [email protected].
PMID: 29550734 DOI: 10.1016/j.ejmech.2018.03.008
Abstract

The synthesis of both 2'-hydroxy-3'-deoxy and 2'-deoxy-3'-hydroxy cyclopentyl nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine and guanine from a single precursor has been performed. The guanine containing analogues showed Antiviral activity. Especially the 3'-deoxy congener 23 was active, displaying an EC50 of 5.35 μM against TK+ VZV strain and an EC50 of 8.83 μM against TK- VZV strain, besides lacking cytotoxicity. However, the application of phosphonodiamidate prodrug strategy did not lead to a boost in Antiviral activity.

Keywords
Antiviral; Carbocyclic nucleoside; Nucleoside phosphonate; Prodrug.