Uridine 5'-diphosphate glucose analogues. Inhibitors of protein glycosylation that show antiviral activity.
A series of analogues of uridine 5'-diphosphate glucose and uridine 5'-diphosphate glucosamine have been synthesized by reaction of 2,3,4,6-tetra-O-benzyl-, 2,3,4,6-tetra-O-benzoyl-, 2,3,4,6-tetra-O-acetyl-, and 2,3,4,6-tetra-O-palmitoyl-alpha-D-glucopyranose and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranose with chlorosulfonyl isocyanate and 2',3'-O-isopropylideneuridine. Isopropylidene and acetyl groups of the resulting 5'-O-[[[[(alpha-D-glucopyranosyl)oxy]carbonyl]amino]sulfonyl] -2',3'-O-isopropylideneuridine derivatives were removed by reaction with a TFA/water (5:1) mixture and methanolic ammonia, respectively. The 5'-O-[[[[(2",3",4",6"-tetra-O-benzyl-and 2",3",4",6"-tetra-O-benzoyl-alpha-D-glucopyranosyl)oxy]carbonyl] amino]sulfonyl]-2',3'-O-isopropylideneuridine (13 and 19) and the corresponding deisopropylidenated derivatives showed antiviral activity as determined by the inhibition of the cytopathic effect induced by HSV-1 replication and by the plaque assay method. Compound 13 inhibited glycosylation of proteins in HSV-1 infected HeLa cells.
Camarasa
M J
MJ
Fernández-Resa
P
P
Garcia-López
M T
MT
De las Heras
F G
FG
Méndez-Castrillón
P P
PP
Alarcón
B
B
Carrasco
L
L
D000998:Antiviral Agents / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011506:Proteins / Q000378:metabolism*; D018139:Simplexvirus / Q000187:drug effects; D014532:Uridine Diphosphate Glucose / Q000031:analogs & derivatives / Q000494:pharmacology*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D014539:Uridine Diphosphate Sugars / Q000494:pharmacology*
D000998:Antiviral Agents; D011506:Proteins; D014539:Uridine Diphosphate Sugars; D014537:Uridine Diphosphate N-Acetylglucosamine; D014532:Uridine Diphosphate Glucose