367258-46-6Relevant articles and documents
Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid
Venkatraman, Srikanth,Njoroge, F. George,Wu, Wanli,Girijavallabhan, Viyyoor,Prongay, Andrew J.,Butkiewicz, Nancy,Pichardo, John
, p. 1628 - 1632 (2007/10/03)
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 ～3000 amino acids that is processed with the help of a serine protease NS3A to prod
Discovery of SCH446211 (SCH6): A new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication
Bogen, Stéphane L.,Arasappan, Ashok,Bennett, Frank,Chen, Kevin,Jao, Edwin,Liu, Yi-Tsung,Lovey, Raymond G.,Venkatraman, Srikanth,Pan, Weidong,Parekh, Tajel,Pike, Russel E.,Ruan, Sumei,Liu, Rong,Baroudy, Bahige,Agrawal, Sony,Chase, Robert,Ingravallo, Paul,Pichardo, John,Prongay, Andrew,Brisson, Jean-Marc,Hsieh, Tony Y.,Cheng, Kuo-Chi,Kemp, Scott J.,Levy, Odile E.,Lim-Wilby, Marguerita,Tamura, Susan Y.,Saksena, Anil K.,Girijavallabhan, Viyyoor,Njoroge, F. George
, p. 2750 - 2757 (2007/10/03)
Introduction of various modified prolines at P2 and optimization of the P1 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 (Ki* = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC50 and IC90 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.
