Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-Guanidino-Neu5Ac2en (Zanamivir) modified in the glycerol side-chain.
Analogues of 4-Guanidino-Neu5Ac2en (Zanamivir) have been prepared containing carbamate substituents at the 7-hydroxy position. (4S,5R,6R)-5-Acetylamino-6-[1R-[(6-aminohexyl)carbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro-4H-pyran-2carboxylic acid and (4S,5R,6R)-5-Acetylamino-6-[1R-[heptylcarbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro4H-pyran2-carboxylic acid were the two analogues possessing activity comparable to Zanamivir, showing potent inhibition of influenza virus sialidases and good antiviral activity in vitro.
Andrews
D M
DM
Department of Medicinal Chemistry, Glaxo-Wellcome Medicines Research Centre, Gunnels Wood Road, Herts, SG1 2NY, Stevenage, UK.
Cherry
P C
PC
Humber
D C
DC
Jones
P S
PS
Keeling
S P
SP
Martin
P F
PF
Shaw
C D
CD
Swanson
S
S
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005990:Glycerol / Q000737:chemistry; D006146:Guanidines; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology*; D009981:Influenza B virus / Q000187:drug effects / Q000201:enzymology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011714:Pyrans; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D010948:Viral Plaque Assay; D053243:Zanamivir
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D009439:Neuraminidase; D053243:Zanamivir; D005990:Glycerol