1. Academic Validation
  2. Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents

Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents

  • ACS Med Chem Lett. 2014 Apr 10;5(6):679-84. doi: 10.1021/ml500077j.
Alistair G Draffan 1 Barbara Frey 1 Brett Pool 1 Carlie Gannon 1 Edward M Tyndall 1 Michael Lilly 1 Paula Francom 1 Richard Hufton 1 Rosliana Halim 1 Saba Jahangiri 1 Silas Bond 1 Van T T Nguyen 1 Tyrone P Jeynes 1 Veronika Wirth 1 Angela Luttick 1 Danielle Tilmanis 1 Jesse D Thomas 1 Melinda Pryor 1 Kate Porter 1 Craig J Morton 1 Bo Lin 1 Jianmin Duan 2 George Kukolj 2 Bruno Simoneau 2 Ginette McKercher 2 Lisette Lagacé 2 Ma'an Amad 2 Richard C Bethell 2 Simon P Tucker 1
Affiliations

Affiliations

  • 1 Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
  • 2 Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
Abstract

Nucleoside analogues have long been recognized as prospects for the discovery of direct acting antivirals (DAAs) to treat hepatitis C virus because they have generally exhibited cross-genotype activity and a high barrier to resistance. C-Nucleosides have the potential for improved metabolism and pharmacokinetic properties over their N-nucleoside counterparts due to the presence of a strong carbon-carbon glycosidic bond and a non-natural heterocyclic base. Three 2'CMe-C-adenosine analogues and two 2'CMe-guanosine analogues were synthesized and evaluated for their anti-HCV efficacy. The nucleotide triphosphates of four of these analogues were found to inhibit the NS5B polymerase, and adenosine analogue 1 was discovered to have excellent pharmacokinetic properties demonstrating the potential of this drug class.

Keywords

C-Nucleoside; HCV; NS5B polymerase.

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