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: piet.herdewijn@kuleuven.be.

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.

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