Synthesis of analogues of the O-beta-D-ribofuranosyl nucleoside moiety of liposidomycins. Part 2: role of the hydroxyl groups upon the inhibition of MraY.
O-beta-D-ribofuranosyl nucleoside I is the minimal structural entity of liposidomycins that maintains enzyme inhibitory activity on MraY. A set of compounds with hydroxyl patterns different from I has been synthesized. The presence of a hydroxyl group in the 3" position is essential for the activity. The 3'-deoxy derivative (IV), however, shows a 5-fold improved potency.
Dini
C
C
Medicinal Chemistry Department, Aventis Pharma, Romainville, France. christophe.dini@aventis.com
Drochon
N
N
Guillot
J C
JC
Mauvais
P
P
Walter
P
P
Aszodi
J
J
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014166:Transferases; D017855:Transferases (Other Substituted Phosphate Groups)
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C047544:liposidomycins; D014166:Transferases; D017855:Transferases (Other Substituted Phosphate Groups); C079803:mraY protein, Bacteria