1,5-Benzodiazepine inhibitors of HCV NS5B polymerase

Autor:	David McGowan, Origène Nyanguile, Maxwell D. Cummings, Sandrine Vendeville, Koen Vandyck, Walter Van den Broeck, Carlo W. Boutton, Hendrik De Bondt, Ludo Quirynen, Katie Amssoms, Jean-François Bonfanti, Stefaan Last, Klara Rombauts, Abdellah Tahri, Lili Hu, Frédéric Delouvroy, Katrien Vermeiren, Geneviève Vandercruyssen, Liesbet Van der Helm, Erna Cleiren, Wendy Mostmans, Pedro Lory, Geert Pille, Kristof Van Emelen, Gregory Fanning, Frederik Pauwels, Tse-I Lin, Kenneth Simmen, Pierre Raboisson
Přispěvatelé:	Analytical Chemistry and Pharmaceutical Technology
Rok vydání:	2009
Předmět:	Stereochemistry Chemistry Pharmaceutical Hepacivirus Hepatitis C virus Clinical Biochemistry Pharmaceutical Science Viral Nonstructural Proteins Crystallography X-Ray medicine.disease_cause Antiviral Agents Biochemistry Virus Hepatitis-C Benzodiazepines Inhibitory Concentration 50 Structure-Activity Relationship Flaviviridae Drug Discovery medicine Humans Replicon Molecular Biology Polymerase Benzodiazepine Molecular Structure biology Chemistry Organic Chemistry Hepatitis C biology.organism_classification Nucleotidyltransferase medicine.disease Virology Acrylates Models Chemical Drug Design HCV biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:2492-2496
ISSN:	0960-894X
Popis:	Optimization through parallel synthesis of a novel series of hepatitis C virus (HCV) NS5B polymerase inhibitors led to the identification of ( R )-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(6-methylpyridine-2-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[ b,e ][1,4]diazepin-1-one 11zc and ( R )-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(2,5-dimethyloxazol-4-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[ b,e ][1,4]diazepin-1-one 11zk as potent (replicon EC 50 = 400 nM and 270 nM, respectively) and selective (CC 50 > 20 μM) inhibitors of HCV replication. These data warrant further lead-optimization efforts.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8521efff0fc4c0c065284cf8f74ff171 https://doi.org/10.1016/j.bmcl.2009.03.035 Zobrazit plný text záznamu Full Text from ScienceDirect