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

Autor:	Tran Chinh Viet, Charles R. Kissinger, Daniel A. Norris, Ruhi Kamran, Amit M. Shah, Jingjing Zhao, Yuefen Zhou, Rupal Patel, Matthew Lardy, Darian M. Bartkowski, Richard E. Showalter, Stephen E. Webber, Laurie A. LeBrun, Mei Tsan, Douglas E. Murphy, Sun Hee Kim, Maria V. Sergeeva, Leo Kirkovsky, Martin T. Tran, Thomas G. Nolan, Qing Han, Frank Ruebsam, Lian-Sheng Li, Peter S. Dragovich
Rok vydání:	2008
Předmět:	Models Molecular Hepatitis C virus Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Viral Nonstructural Proteins Crystallography X-Ray medicine.disease_cause Antiviral Agents Biochemistry Cell Line Structure-Activity Relationship Drug Discovery medicine Animals Humans Transferase Structure–activity relationship Pyrroles Replicon Molecular Biology chemistry.chemical_classification Binding Sites Molecular Structure biology Chemistry Organic Chemistry Hydrogen Bonding Nucleotidyltransferase In vitro Pyridazines Enzyme Enzyme inhibitor biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 18:3616-3621
ISSN:	0960-894X
Popis:	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 3 k, which displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b)10nM; EC(50) (1b)=12 nM) as well as good stability towards human liver microsomes (HLM t(1/2)60 min).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f4ad75b76b7814c0968de6c9e82a0a6 https://doi.org/10.1016/j.bmcl.2008.04.066 Zobrazit plný text záznamu Full Text from ScienceDirect