| Literature DB >> 24944743 |
Alistair G Draffan1, Barbara Frey1, Brett Pool1, Carlie Gannon1, Edward M Tyndall1, Michael Lilly1, Paula Francom1, Richard Hufton1, Rosliana Halim1, Saba Jahangiri1, Silas Bond1, Van T T Nguyen1, Tyrone P Jeynes1, Veronika Wirth1, Angela Luttick1, Danielle Tilmanis1, Jesse D Thomas1, Melinda Pryor1, Kate Porter1, Craig J Morton1, Bo Lin1, Jianmin Duan2, George Kukolj2, Bruno Simoneau2, Ginette McKercher2, Lisette Lagacé2, Ma'an Amad2, Richard C Bethell2, Simon P Tucker1.
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.Entities:
Keywords: C-Nucleoside; HCV; NS5B polymerase
Year: 2014 PMID： 24944743 PMCID： PMC4060939 DOI： 10.1021/ml500077j
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345