Abstract
SAR investigations of the 4- and 5-positions of a series of 4-amino-4H-pyran-2-carboxylic acid 6-carboxamides are reported. Potent inhibitors of influenza A sialidase with marked selectivity over the influenza B enzyme were obtained when the basic 4-amino substituent was replaced by hydroxyl or even deleted. Modifications at the 5-position exhibited a tight steric requirement, with trifluoroacetamide being optimal.
MeSH terms
-
Antiviral Agents / chemical synthesis
-
Antiviral Agents / chemistry*
-
Antiviral Agents / pharmacology
-
Binding Sites
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology
-
Guanidines
-
Influenza A virus / drug effects
-
Influenza A virus / enzymology
-
Influenza B virus / drug effects
-
Influenza B virus / enzymology
-
Models, Molecular
-
Molecular Structure
-
Neuraminidase / antagonists & inhibitors
-
Neuraminidase / metabolism
-
Nylons / chemistry*
-
Nylons / pharmacology
-
Pyrans / chemistry*
-
Pyrans / pharmacology
-
Sialic Acids / chemistry*
-
Sialic Acids / metabolism
-
Structure-Activity Relationship
-
Viral Plaque Assay
-
Zanamivir
Substances
-
Antiviral Agents
-
Enzyme Inhibitors
-
Guanidines
-
Nylons
-
Pyrans
-
Sialic Acids
-
Neuraminidase
-
Zanamivir