Advances in the Development of Macrocyclic Inhibitors of Hepatitis C Virus NS3-4A Protease

Author(s): Salvatore Avolio, Vincenzo Summa.

Journal Name: Current Topics in Medicinal Chemistry

Volume 10 , Issue 14 , 2010

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Hepatitis C virus (HCV) is a major cause of acute hepatitis and chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). No vaccine is currently available to prevent hepatitis C, and the current standard of care (SOC) – pegylated interferon-α (PEG-IFN-α) in combination with ribavirin (RBV) – is only partially effective and it also presents side effects. Novel treatment options now under intensive development are focused on the discovery of inhibitors of HCV-specific enzymes. The HCV NS3 protease plays an essential role for viral replication and it is recognized as one of the most attractive targets for developing novel anti-HCV therapies. After two decades of research efforts a number of potent active-site inhibitors of the NS3 protease have been generated and some of them are in late stage of clinical trials. A particularly interesting class of HCV NS3 protease inhibitors are based on depeptidized macrocyclic structures. The article reviews the recent progresses made in the discovery and development of macrocyclic inhibitors of the HCV NS3 protease as described in the most recent scientific literature (patent excluded), from a medicinal chemistry perspective.

Keywords: Antivirals, covalent inhibitor, clinical candidates, hepatitis C virus (HCV), macrocycle, NS3, peptide, protease inhibitor

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Article Details

Year: 2010
Page: [1403 - 1422]
Pages: 20
DOI: 10.2174/156802610792232051
Price: $58

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