Abstract
We synthesized polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en analogues on the polyglutamic acid back bone, via a spacer of alkyl ether at the C-7 position. These multivalent conjugates 9 and 10 showed enhancement of antiviral activity against infuenza A virus and more potent efficacy in vivo relative to a monomeric sialidase inhibitor.
MeSH terms
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Animals
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Antiviral Agents / chemistry*
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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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Glutamic Acid / chemistry
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Glyceryl Ethers / chemistry
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Guanidine / analogs & derivatives*
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Guanidine / chemical synthesis
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Guanidine / 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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Mice
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N-Acetylneuraminic Acid / analogs & derivatives*
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N-Acetylneuraminic Acid / chemistry*
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N-Acetylneuraminic Acid / pharmacology*
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Neuraminidase / antagonists & inhibitors*
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Neuraminidase / chemistry
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Orthomyxoviridae Infections / drug therapy
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Pyrans
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Sialic Acids
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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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2-deoxy-2,3-dehydro-N-acetylneuraminic acid
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Glutamic Acid
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Neuraminidase
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N-Acetylneuraminic Acid
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Guanidine
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Zanamivir