title: Synthesis and evaluation of novel HCV replication inhibitors.
abstract: Direct acting antiviral agents to cure hepatitis C virus (HCV) infection has emerged as the gold standard therapy. Along with protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors, the inhibition of NS5a has proved to be an effective way to treat HCV patients. Here we report on novel HCV NS5a inhibitors which were synthesized and evaluated in the HCV replicon assay. A series of inhibitors were formed by a cycloaddition reaction in parallel to establish new leads and explore the effects of unsymmetrical cap substitution. This led to the identification of several triazoles with picomolar potency in vitro against hepatitis C virus.
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340, Beerse, Belgium. dmcgowan@its.jnj.com.
authors.forename: David C
authors.initials: DC
authors.lastname: McGowan
authors.affiliation: Villapharma Research, Parque Tecnológico de Fuente Álamo, Ctra. El Estrecho-Lobosillo, Km. 2,5- Av. Azul, 30320, Fuente Álamo de Murcia, Murcia, Spain.
authors.forename: Mourad D
authors.initials: MD
authors.lastname: Khamlichi
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Alex
authors.initials: A
authors.lastname: De Groot
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Pauwels
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Delouvroy
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Van Emelen
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Simmen
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Raboisson
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Click chemistry; HCV NS5a; Hepatitis C; Replication inhibitor