Abstract
A series of 7-alkyl ether derivatives related to zanamivir were synthesized using direct alkylation of the C-7 alcohol of sialic acid. Alkyl ether moiety of less than 12 carbons in length showed low nanomolar inhibitory activity against influenza A virus sialidase. Furthermore, their moiety improved influenza A virus plaque reduction activity compared to zanamivir. However, removal of the 8,9-diol of the 7-O-alkyl derivatives resulted in loss of antiviral potency. This result suggests that 8,9-diol must play an important role in binding with both influenza A and B virus sialidases.
MeSH terms
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / pharmacology*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Glyceryl Ethers / chemistry*
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Glyceryl Ethers / pharmacology*
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Guanidines
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Influenza A virus / drug effects*
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Influenza A virus / enzymology
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Inhibitory Concentration 50
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N-Acetylneuraminic Acid / chemistry
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Neuraminidase / antagonists & inhibitors
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Pyrans
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Sialic Acids / chemistry*
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Structure-Activity Relationship
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Viral Plaque Assay
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Zanamivir
Substances
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Antiviral Agents
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Enzyme Inhibitors
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Glyceryl Ethers
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Guanidines
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Pyrans
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Sialic Acids
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Neuraminidase
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N-Acetylneuraminic Acid
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Zanamivir