Potent aza-peptide derived inhibitors of HCV NS3 protease.
Chronic hepatitis C infection is the primary cause for cirrhosis of the liver and hepatocellular carcinoma leading to liver failure and transplantation. The etiological agent hepatitis C virus produces a single positive strand RNA that is processed further with the help of NS3 serine protease to produce mature virus. Inhibition of this protease can potentially be used to develop drugs for HCV infections. Boceprevir is a ketoamide derived novel inhibitor of HCV NS3 protease that has been progressed to clinical trials and proven to be efficacious in humans. Herein, we report our efforts in identifying an aza-peptide derivative as a potential second generation compound, that lacks electrophilic ketoamide group and are potent in enzyme and replicon assay.
Venkatraman
Srikanth
S
Schering Plough Research Institute, K15-MS 3545, Kenilworth, NJ 07033, United States. Srikanth.Venkatraman@spcorp.com
Wu
Wanli
W
Shih
Neng-Yang
NY
George Njoroge
F
F
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016174:Hepacivirus / Q000201:enzymology*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D001372:Aza Compounds; D010455:Peptides; 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