Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1 '4'-dihydro-1λ-benzo[1',2',4']thiadiazin-3-yl)-5-hydroxy-2H-pyridazin-3-ones: Part 4. Optimization of DMPK properties

5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties.

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2008-06, Vol.18 (11), p.3421-3426
Main Authors: SERGEEVA, Maria V, YUEFEN ZHOU, PATEL, Rupal, SHAH, Amit M, LARDY, Matthew, GOBBI, Alberto, LI, Lian-Sheng, JINGJING ZHAO, BERTOLINI, Thomas, STANKOVIC, Nebojsa, ZHONGXIANG SUN, MURPHY, Douglas E, BARTKOWSKI, Darian M, WEBBER, Stephen E, DRAGOVICH, Peter S, NOLAN, Thomas G, NORRIS, Daniel A, OKAMOTO, Ellen, KIRKOVSKY, Leo, KAMRAN, Ruhi, LEBRUN, Laurie A, TSAN, Mei
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacokinetics
Biological and medical sciences
Combinatorial Chemistry Techniques
Drug Design
Haplorhini
Hepacivirus - enzymology
Inhibitory Concentration 50
Medical sciences
Models, Molecular
Molecular Structure
Pharmacology. Drug treatments
Pyridazines - chemical synthesis
Pyridazines - chemistry
Pyridazines - pharmacokinetics
Structure-Activity Relationship
Viral Nonstructural Proteins - antagonists & inhibitors
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Description
Summary:5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2008.04.005