Pyrrolo[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase

Authors :: Ruebsam, Frank
Webber, Stephen E.
Tran, Martin T.
Tran, Chinh V.
Murphy, Douglas E.
Zhao, Jingjing
Dragovich, Peter S.
Kim, Sun Hee
Li, Lian-Sheng
Zhou, Yuefen
Han, Qing
Kissinger, Charles R.
Showalter, Richard E.
Lardy, Matthew
Shah, Amit M.
Tsan, Mei
Patel, Rupal
LeBrun, Laurie A.
Kamran, Ruhi
Sergeeva, Maria V.
Source :: Bioorganic & Medicinal Chemistry Letters. Jun2008, Vol. 18 Issue 12, p3616-3621. 6p.
Publication Year :: 2008
Abstract: Abstract: Pyrrolo[1,2-b]pyridazin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Structure-based design led to the discovery of compound 3k, which displayed potent inhibitory activities in biochemical and replicon assays (IC50 (1b)<10nM; EC50 (1b)=12nM) as well as good stability towards human liver microsomes (HLM t 1/2 >60min). [Copyright &y& Elsevier]