Abstract
Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that size and geometry of the C3-side chain are important for selectivity of inhibition against N1 versus N2 NA, important type A influenza variants that infect man, including the highly lethal avian influenza.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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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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Benzoic Acid / chemical synthesis
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Benzoic Acid / chemistry*
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Benzoic Acid / pharmacology
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Hydrophobic and Hydrophilic Interactions
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Influenza A Virus, H1N1 Subtype / drug effects
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Influenza A Virus, H3N2 Subtype / drug effects
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Influenza A virus / drug effects
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Influenza A virus / enzymology*
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Neuraminidase / antagonists & inhibitors*
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Neuraminidase / metabolism
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Pyrrolidinones / chemistry*
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Structure-Activity Relationship
Substances
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Antiviral Agents
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Enzyme Inhibitors
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Pyrrolidinones
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Benzoic Acid
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Neuraminidase