Journal article
Discovery and synthesis of c-nucleosides as potential new anti-HCV agents
AG Draffan, B Frey, B Pool, C Gannon, EM Tyndall, M Lilly, P Francom, R Hufton, R Halim, S Jahangiri, S Bond, VTT Nguyen, TP Jeynes, V Wirth, A Luttick, D Tilmanis, JD Thomas, M Pryor, K Porter, CJ Morton Show all
ACS Medicinal Chemistry Letters | AMER CHEMICAL SOC | Published : 2014
DOI: 10.1021/ml500077j
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..
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