Molecular Modeling Based Approach to Potent P2-P4 Macrocyclic Inhibitors of Hepatitis C NS3/4A Protease

Molecular Modeling Based Approach to Potent P2-P4 Macrocyclic Inhibitors of Hepatitis C NS3/4A Protease

Molecular modeling of inhibitor bound full length HCV NS3/4A protease structures proved to be a valuable tool in the design of a new series of potent NS3 protease inhibitors. Optimization of initial compounds provided 25a. The in vitro activity and selectivity as well as the rat pharmacokinetic prof...

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Veröffentlicht in:Journal of the American Chemical Society 2008-01, Vol.130 (14), p.4607-4609
Hauptverfasser: Liverton, Nigel J, Holloway, MKatharine, McCauley, John A, Rudd, Michael T, Butcher, John W, Carroll, Steven S, DiMuzio, Jillian, Fandozzi, Christine, Gilbert, Kevin F, Mao, Shi-Shan, McIntyre, Charles J, Nguyen, Kevin T, Romano, Joseph J, Stahlhut, Mark, Wan, Bang-Lin, Olsen, David B, Vacca, Joseph P
Format: Artikel
Sprache:eng
Schlagworte:
Hepatitis C virus
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Zusammenfassung:Molecular modeling of inhibitor bound full length HCV NS3/4A protease structures proved to be a valuable tool in the design of a new series of potent NS3 protease inhibitors. Optimization of initial compounds provided 25a. The in vitro activity and selectivity as well as the rat pharmacokinetic profile of 25a compare favorably with the data for other NS3/4A protease inhibitors currently in clinical development for the treatment of HCV.
ISSN:1272-7863
1520-5126
DOI:10.1021/ja711120rPII:S0002-7863(71)01120-X