title: Imidazo[1,2-a]pyridines That Directly Interact with Hepatitis C NS4B: Initial Preclinical Characterization.
abstract: A series of imidazo[1,2-a]pyridines which directly bind to HCV Non-Structural Protein 4B (NS4B) is described. This series demonstrates potent in vitro inhibition of HCV replication (EC50 < 10 nM), direct binding to purified NS4B protein (IC50 < 20 nM), and an HCV resistance pattern associated with NS4B (H94N/R, V105L/M, F98L) that are unique among reported HCV clinical assets, suggestive of the potential for additive or synergistic combination with other small molecule inhibitors of HCV replication.
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: J Brad
authors.initials: JB
authors.lastname: Shotwell
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Baskaran
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Pek
authors.initials: P
authors.lastname: Chong
authors.affiliation: GlaxoSmithKline , Platform Technology and Science, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Creech
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Renae M
authors.initials: RM
authors.lastname: Crosby
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Hamilton
authors.initials: H
authors.lastname: Dickson
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Dulce
authors.initials: D
authors.lastname: Garrido
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mathis
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Jack
authors.initials: J
authors.lastname: Maung
authors.affiliation: GlaxoSmithKline , Platform Technology and Science, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Parks
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Pouliot
authors.affiliation: GlaxoSmithKline , Platform Technology and Science, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Price
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Roopa
authors.initials: R
authors.lastname: Rai
authors.affiliation: GlaxoSmithKline , Platform Technology and Science, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Seal
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Uli
authors.initials: U
authors.lastname: Schmitz
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Vincent W F
authors.initials: VW
authors.lastname: Tai
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomson
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Mi
authors.initials: M
authors.lastname: Xie
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Zhiping Z
authors.initials: ZZ
authors.lastname: Xiong
authors.affiliation: GlaxoSmithKline , Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Peat
keywords: NS4B; hepatitis C virus; imidazo[1,2-a]pyridines; replicon