Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. Part 7: Structure–Activity Studies of Bicyclic 2-Pyridone-Containing Peptidomimetics

• Published in: Bioorganic & medicinal chemistry letters 2002-03, Vol.12 (5), p.733-738
• Main Authors: Dragovich, Peter S., Prins, Thomas J., Zhou, Ru, Johnson, Theodore O., Brown, Edward L., Maldonado, Fausto C., Fuhrman, Shella A., Zalman, Leora S., Patick, Amy K., Matthews, David A., Hou, Xinjun, Meador, James W., Ferre, Rose Ann, Worland, Stephen T.
• Format: Article
• Language: English
• Subjects: 3C Viral Proteases; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis; Bridged Bicyclo Compounds, Heterocyclic - chemistry; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Cell Line; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors - chemical synthesis; Cysteine Proteinase Inhibitors - pharmacology; Drug Design; Humans; Medical sciences; Molecular Mimicry; Pharmacology. Drug treatments; Pyridones - chemical synthesis; Pyridones - chemistry; Pyridones - pharmacology; Rhinovirus - drug effects; Rhinovirus - enzymology; Serotyping; Structure-Activity Relationship; Viral Proteins - antagonists & inhibitors
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00008-2

The structure-based design, chemical synthesis, and biological evaluation of bicyclic 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. An optimized compound is shown to exhibit antiviral activity when tested against a variety of HRV serotypes (EC 50's ranging from 0.037 to 0.162 μM). Graphic