Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides.
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.
Department of Medicinal Chemistry, Glaxo Wellcome Medicines Research Centre, Stevenage, Herts, UK. pw29967@glaxowellcome.co.uk
P G
PG
Wyatt
B A
BA
Coomber
D N
DN
Evans
T I
TI
Jack
H E
HE
Fulton
A J
AJ
Wonacott
P
P
Colman
J
J
Varghese
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006146:Guanidines; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology; D009981:Influenza B virus / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009757:Nylons / Q000737:chemistry* / Q000494:pharmacology; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay; D053243:Zanamivir
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D009757:Nylons; D011714:Pyrans; D012794:Sialic Acids; D009439:Neuraminidase; D053243:Zanamivir