Imidazo[1,2-a]pyridines That Directly Interact with Hepatitis C NS4B: Initial Preclinical Characterization

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• 作者：J. Brad Shotwell ; Subramanian Baskaran ; Pek Chong ; Katrina L. Creech ; Renae M. Crosby ; Hamilton Dickson ; Jing Fang ; Dulce Garrido ; Amanda Mathis ; Jack Maung ; Derek J. Parks ; Jeffrey J. Pouliot ; Daniel J. Price ; Roopa Rai ; John W. Seal ; III ; Uli Schmitz ; Vincent W. F. Tai ; Michael Thomson ; Mi Xie ; Zhiping Z. Xiong ; Andrew J. Peat
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：July 12, 2012
• 年：2012
• 卷：3
• 期：7
• 页码：565-569
• 全文大小：283K
• 年卷期：v.3,no.7(July 12, 2012)
• ISSN：1948-5875

文摘

A series of imidazo[1,2-a]pyridines which directly bind to HCV Non-Structural Protein 4B (NS4B) is described. This series demonstrates potent in vitro inhibition of HCV replication (EC₅₀ < 10 nM), direct binding to purified NS4B protein (IC₅₀ < 20 nM), and an HCV resistance pattern associated with NS4B (H94N/R, V105L/M, F98L) that are unique among reported HCV clinical assets, suggestive of the potential for additive or synergistic combination with other small molecule inhibitors of HCV replication.

Keywords:

p://pubs.acs.org/action/doSearch?action=search&searchText=NS4B&qsSearchArea=searchText">NS4B; p://pubs.acs.org/action/doSearch?action=search&searchText=hepatitis+C+virus&qsSearchArea=searchText">hepatitis C virus; p://pubs.acs.org/action/doSearch?action=search&searchText=imidazo%5C%5B1%2C2%5C-a%5C%5Dpyridines&qsSearchArea=searchText">imidazo[1,2-a]pyridines; p://pubs.acs.org/action/doSearch?action=search&searchText=replicon&qsSearchArea=searchText">replicon