Molecular Modeling Based Approach to Potent P2-P4 Macrocyclic Inhibitors of Hepatitis C NS3/4A Protease
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- 作者：Nigel J. Liverton ; M. Katharine Holloway ; John A. McCauley ; Michael T. Rudd ; John W. Butcher ; Steven S. Carroll ; Jillian DiMuzio ; Christine Fandozzi ; Kevin F. Gilbert ; Shi-Shan Mao ; Charles J. McIntyr
- 刊名：Journal of the American Chemical Society
- 出版年：2008
- 出版时间：April 9, 2008
- 年：2008
- 卷：130
- 期：14
- 页码：4607 - 4609
- 全文大小：378K
- 年卷期：v.130,no.14(April 9, 2008)
- ISSN：1520-5126
文摘
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.