Abstract
West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. These compounds degrade rapidly in pH 8 buffer with a half life of 1-2h. We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Allosteric Regulation
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Antiviral Agents / chemical synthesis
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Antiviral Agents / chemistry*
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Antiviral Agents / pharmacology
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Drug Design
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Half-Life
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Hydrogen-Ion Concentration
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Hydrolysis
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry*
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Pyrazoles / pharmacology
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RNA Helicases / antagonists & inhibitors
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RNA Helicases / metabolism
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Serine Endopeptidases / metabolism
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Serine Proteinase Inhibitors / chemical synthesis
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Serine Proteinase Inhibitors / chemistry*
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / metabolism
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West Nile Fever / drug therapy
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West Nile virus / drug effects*
Substances
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Antiviral Agents
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NS2B protein, flavivirus
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NS3 protein, flavivirus
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Pyrazoles
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Serine Proteinase Inhibitors
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Viral Nonstructural Proteins
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Serine Endopeptidases
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RNA Helicases