title: Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity.
abstract: Depeptidization efforts of the P(3)-P(2) region of P(3) capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 are reported. We clearly established that N-methylation of the P(2) nitrogen and modification of the P(2)' carboxylic acid terminus were essential for activity in the replicon assay.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. stephane.bogen@spcorp.com
authors.forename: Stéphane L
authors.initials: SL
authors.lastname: Bogen
authors.forename: Sumei
authors.initials: S
authors.lastname: Ruan
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Sony
authors.initials: S
authors.lastname: Agrawal
authors.forename: John
authors.initials: J
authors.lastname: Pichardo
authors.forename: Andrew
authors.initials: A
authors.lastname: Prongay
authors.forename: Bahige
authors.initials: B
authors.lastname: Baroudy
authors.forename: Anil K
authors.initials: AK
authors.lastname: Saksena
authors.forename: Viyyoor
authors.initials: V
authors.lastname: Girijavallabhan
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D016174:Hepacivirus / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008745:Methylation; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D011485:Protein Binding; D012093:Replicon / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014961:X-Ray Diffraction; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000577:Amides; D009584:Nitrogen; D015842:Serine Proteinase 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