Synthesis and SAR of piperazinyl-N-phenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture.
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.
Conte
Immacolata
I
Department of Medicinal Chemistry, Istituto di Ricerche di Biologia Molecolare "P. Angeletti" S.p.A., Merck Research Laboratories Rome, 00040 Pomezia, Rome, Italy.
Giuliano
Claudio
C
Ercolani
Caterina
C
Narjes
Frank
F
Koch
Uwe
U
Rowley
Michael
M
Altamura
Sergio
S
De Francesco
Raffaele
R
Neddermann
Petra
P
Migliaccio
Giovanni
G
Stansfield
Ian
I
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*
D000998:Antiviral Agents; D001549:Benzamides; D017361:Viral Nonstructural Proteins; D007372:Interferons; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase