title: Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: discovery, initial SAR, and molecular modeling.
abstract: The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.
authors.affiliation: Department of Chemistry, IRBM--MRL Rome, Via Pontina Km 30.600, 00040 Pomezia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Colarusso
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gerlach
authors.forename: Christian
authors.initials: C
authors.lastname: Steinkühler
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.forename: Sergio
authors.initials: S
authors.lastname: Altamura
authors.forename: Victor G
authors.initials: VG
authors.lastname: Matassa
authors.forename: Frank
authors.initials: F
authors.lastname: Narjes
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000577:Amides; D001555:Benzene Derivatives; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases