Discovery of SCH446211 (SCH6): A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication
Introduction of various modified prolines at P{sub 2} and optimization of the P{sub 1} side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K*{sub i} = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC{sub 50} and IC{sub 90} of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1007778
- Journal Information:
- J. Med. Chem., Journal Name: J. Med. Chem. Journal Issue: (9) ; 05, 2006 Vol. 49; ISSN JMCMAR; ISSN 0022-2623
- Country of Publication:
- United States
- Language:
- ENGLISH
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