Document Report Card

ID: ALA3286396

Journal: ACS Med Chem Lett

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

Authors: Draffan AG, Frey B, Pool B, Gannon C, Tyndall EM, Lilly M, Francom P, Hufton R, Halim R, Jahangiri S, Bond S, Nguyen VT, Jeynes TP, Wirth V, Luttick A, Tilmanis D, Thomas JD, Pryor M, Porter K, Morton CJ, Lin B, Duan J, Kukolj G, Simoneau B, McKercher G, Lagacé L, Amad M, Bethell RC, Tucker SP.

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.

CiteXplore: 24944743

DOI: 10.1021/ml500077j