title: Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid.
abstract: Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver and hepatocellular carcinoma. The etiological agent HCV virus codes a single polyprotein of approximately 3000 amino acids that is processed with the help of a serine protease NS3A to produce structural and non-structural proteins required for viral replication. Inhibition of NS3 protease can potentially be used to develop drugs for treatment of HCV infections. Herein, we report the development of a series of novel NS3 serine protease inhibitors derived from 2-aza-bicyclo[2.2.1]-heptane carboxylic acid with potential therapeutic use for treatment of HCV infections.
authors.affiliation: Schering Plough Research Institute, K-15, MS-3545, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. Srikanth.Venkatraman@spcorp.com
authors.forename: Srikanth
authors.initials: S
authors.lastname: Venkatraman
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge
authors.forename: Wanli
authors.initials: W
authors.lastname: Wu
authors.forename: Viyyoor
authors.initials: V
authors.lastname: Girijavallabhan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Prongay
authors.forename: Nancy
authors.initials: N
authors.lastname: Butkiewicz
authors.forename: John
authors.initials: J
authors.lastname: Pichardo
mesh_terms: D001665:Binding Sites; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D015394:Molecular Structure; 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: D001643:Bridged Bicyclo Compounds; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C095673:2-azabicyclo(2.2.1)heptane-3-carboxylic acid; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases