Abstract
A series of pyrrolidine derivatives were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially 4-hydroxy-L-proline using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A neuraminidase. Within this series, five compounds, 6e, 9c, 9e, 9f, and 10e, have good potency (IC(50)=1.56-2.71 microM) which are compared to that the NA inhibitor Oseltamivir (IC(50)=1.06 microM), and could be used as lead compoundS in the future.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Diclofenac / pharmacology
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Hydroxyproline / chemistry
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Hydroxyproline / pharmacology
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Indicators and Reagents
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Influenza A Virus, H3N2 Subtype / drug effects
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Influenza A Virus, H3N2 Subtype / enzymology*
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Neuraminidase / antagonists & inhibitors*
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / pharmacology*
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Spectrometry, Mass, Electrospray Ionization
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Spectrophotometry, Ultraviolet
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Enzyme Inhibitors
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Indicators and Reagents
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Pyrrolidines
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Diclofenac
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Neuraminidase
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Hydroxyproline