title: Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with improved potency.
abstract: We have discovered that introduction of appropriate amino acid derivatives at P'2 position improved the binding potency of P3-capped alpha-ketoamide inhibitors of HCV NS3 serine protease. X-ray crystal structure of one of the inhibitors (43) bound to the protease revealed the importance of the P'2 moiety.
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ashok.arasappan@spcorp.com
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authors.lastname: Arasappan
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authors.lastname: Njoroge
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authors.lastname: Chan
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authors.initials: F
authors.lastname: Bennett
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authors.lastname: Bogen
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authors.lastname: Chen
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authors.lastname: Hong
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authors.lastname: Jao
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authors.lastname: Liu
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authors.lastname: Lovey
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authors.lastname: Parekh
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authors.lastname: Pike
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authors.lastname: Pinto
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authors.lastname: Santhanam
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authors.lastname: Venkatraman
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authors.lastname: Vaccaro
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authors.lastname: Wang
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authors.lastname: Yang
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authors.lastname: Zhu
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authors.initials: B
authors.lastname: Mckittrick
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authors.lastname: Saksena
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authors.lastname: Girijavallabhan
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authors.lastname: Pichardo
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authors.lastname: Butkiewicz
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authors.lastname: Ingram
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authors.lastname: Malcolm
authors.forename: A
authors.initials: A
authors.lastname: Prongay
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authors.lastname: Yao
authors.forename: B
authors.initials: B
authors.lastname: Marten
authors.forename: V
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authors.lastname: Madison
authors.forename: S
authors.initials: S
authors.lastname: Kemp
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authors.lastname: Levy
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authors.lastname: Lim-Wilby
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authors.lastname: Tamura
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authors.lastname: Ganguly
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D016174:Hepacivirus / Q000737:chemistry*; D015394:Molecular Structure; D011485:Protein Binding; D015842:Serine Proteinase Inhibitors / 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: 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