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5,5 '- and 6,6 '-Dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase

  作者 Ellis, DA; Blazel, JK; Tran, CV; Ruebsam, F; Murphy, DE; Li, LS; Zhao, JJ; Zhou, YF; McGuire, HM; Xiang, AX; Webber, SE; Zhao, Q; Han, Q; Kissinger, CR; Lardy, M; Gobbi, A; Showalter, RE; Shah, AM; Tsan, M; Patel, RA; LeBrun, LA; Kamran, R; Bartkowski, DM; Nolan, TG; Norris, DA; Sergeeva, MV; Kirkovsky, L  
  选自 期刊  Bioorganic & Medicinal Chemistry Letters;  卷期  2009年19-21;  页码  6047-6052  
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[摘要]The discovery of 5,5 '- and 6,6 '-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC50 <0.10 mu M). In vitro DMPK data for selected compounds as well as crystal structures of representative inhibitors complexed with the NS5B protein are also disclosed. (C) 2009 Elsevier Ltd. All rights reserved.

 
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