title: Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents.
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.
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Draffan
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Frey
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Pool
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Carlie
authors.initials: C
authors.lastname: Gannon
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Tyndall
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Lilly
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Francom
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Hufton
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Rosliana
authors.initials: R
authors.lastname: Halim
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Saba
authors.initials: S
authors.lastname: Jahangiri
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Silas
authors.initials: S
authors.lastname: Bond
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Van T T
authors.initials: VT
authors.lastname: Nguyen
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Tyrone P
authors.initials: TP
authors.lastname: Jeynes
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Veronika
authors.initials: V
authors.lastname: Wirth
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Luttick
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Danielle
authors.initials: D
authors.lastname: Tilmanis
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Thomas
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Melinda
authors.initials: M
authors.lastname: Pryor
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Porter
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Morton
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
authors.affiliation: Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
authors.forename: Bruno
authors.initials: B
authors.lastname: Simoneau
authors.affiliation: Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
authors.forename: Ginette
authors.initials: G
authors.lastname: McKercher
authors.affiliation: Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
authors.forename: Lisette
authors.initials: L
authors.lastname: Lagacé
authors.affiliation: Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
authors.forename: Ma'an
authors.initials: M
authors.lastname: Amad
authors.affiliation: Research and Development, Boehringer Ingelheim (Canada), Ltd. , 2100 rue Cunard, Laval, Québec H7S 2G5, Canada.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Bethell
authors.affiliation: Biota Scientific Management Pty. Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Tucker
keywords: C-Nucleoside; HCV; NS5B polymerase