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Your search keyword '"Katrien Vermeiren"' showing total 2 results
Start Over Author "Katrien Vermeiren" Publisher elsevier bv
2 results on '"Katrien Vermeiren"'

1. 1,5-Benzodiazepine inhibitors of HCV NS5B polymerase

Author

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, and Analytical Chemistry and Pharmaceutical Technology

Subjects
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
Abstract

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.

Published
2009
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2. Evaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors

Author

Frederic Delouvroy, Katrien Vermeiren, Dominique Louis Nestor Ghislain Surleraux, Sarvajit Chakravarty, Annick Scholliers, Pierre Raboisson, Tse-I Lin, Thierry Verbinnen, Kenneth Simmen, and Oliver Lenz

Subjects
Male, MAP Kinase Kinase 4, Chemistry, Pharmaceutical, Clinical Biochemistry, Molecular Conformation, Pharmaceutical Science, Hepacivirus, Viral Nonstructural Proteins, Pharmacology, Antiviral Agents, Biochemistry, Cell Line, Inhibitory Concentration 50, Mice, Growth factor receptor, Drug Discovery, Animals, Humans, Luciferase, Replicon, Enzyme Inhibitors, Protein kinase A, NS5A, Molecular Biology, Vascular Endothelial Growth Factor Receptor-1, biology, Kinase, Chemistry, Organic Chemistry, Models, Chemical, Evaluation Studies as Topic, Area Under Curve, Drug Design, Mitogen-activated protein kinase, biology.protein, Molecular Medicine, Signal transduction
Abstract

Screening of a focused library of TGF beta kinase inhibitors in the cellular HCV replicon model with luciferase read out yielded a number of low micromolar HCV inhibitors. Medicinal chemistry driven optimization resulted in the discovery of 4-[2-(5-bromo-2-fluoro-phenyl)pteridin-4-ylamino]-N-[3-(2- oxopyrrolidin-1-yl)propyl]nicotinamide 36 with a replicon EC50 of 64 nM, associated with a selective kinase inhibitory profile for human JNK kinases 2 and 3 as well as VEGFR-1, 2, and 3 kinases. Moreover, 36 showed an advantageous PK profile in mice. Experiments performed using different replicon constructs suggest that this series of kinase inhibitors might mediate their effect through the HCV non-structural protein 5A (NS5A).

Published
2007
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