- 4-AMINO-4-OXOBUTANOYL PEPTIDES AS INHIBITORS OF VIRAL REPLICATION
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The invention provides 4-amino-4-oxobutanoyl peptide compounds of Formula I and the pharmaceutically salts and hydrates thereof. The variables R1-R9, R16, R18, R19, n, M, n, M, and Z are defined herein. Certain compounds of Formula I are useful as antiviral agents. Certain 4-amino-4-oxobutanoyl peptide compounds disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. The invention also provides pharmaceutical compositions containing one or more 4-amino-4-oxobutanoyl peptide compounds and one or more pharmaceutically acceptable carriers. Such pharmaceutical compositions may contain 4-amino-4-oxobutanoyl peptide compound as the only active agent or may contain a combination of 4-amino-4-oxobutanoyl peptide containing peptides compound and one or more other pharmaceutically active agents. The invention also provides methods for treating viral infections, including Hepatitis C infections, in mammals.
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Page/Page column 34-35
(2009/03/07)
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- Potent inhibitors of the hepatitis C virus NS3 protease: Design and synthesis of macrocyclic substrate-based β-strand mimics
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The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring β-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.
- Goudreau, Nathalie,Brochu, Christian,Cameron, Dale R.,Duceppe, Jean-Simon,Faucher, Anne-Marie,Ferland, Jean-Marie,Grand-Maitre, Chantal,Poirier, Martin,Simoneau, Bruno,Tsantrizos, Youla S.
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p. 6185 - 6201
(2007/10/03)
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