title: Synthesis and SAR of piperazinyl-N-phenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture.
abstract: The RNA replication machinery of HCV is a multi-subunit membrane-associated complex. NS5A has emerged as an active component of HCV replicase, possibly involved in regulation of viral replication and resistance to the antiviral effect of interferon. We report here substituted piperazinyl-N-(aryl)benzamides as potent inhibitors of HCV replication exerted via modulation of the dimerization of NS5A.
authors.affiliation: Department of Medicinal Chemistry, Istituto di Ricerche di Biologia Molecolare "P. Angeletti" S.p.A., Merck Research Laboratories Rome, 00040 Pomezia, Rome, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Conte
authors.forename: Claudio
authors.initials: C
authors.lastname: Giuliano
authors.forename: Caterina
authors.initials: C
authors.lastname: Ercolani
authors.forename: Frank
authors.initials: F
authors.lastname: Narjes
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Sergio
authors.initials: S
authors.lastname: Altamura
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.forename: Petra
authors.initials: P
authors.lastname: Neddermann
authors.forename: Giovanni
authors.initials: G
authors.lastname: Migliaccio
authors.forename: Ian
authors.initials: I
authors.lastname: Stansfield
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray / Q000379:methods; D019281:Dimerization; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D009154:Mutation; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D017361:Viral Nonstructural Proteins; D007372:Interferons; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase