Carbohydroxamido-oxazolidines: antibacterial agents that target lipid A biosynthesis.
A series of carbohydroxamido-oxazolidine inhibitors of UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase, the enzyme responsible for the second step in lipid A biosynthesis, was identified. The most potent analog L-161,240 showed an IC50 = 30 nM in the DEACET assay and displayed an MIC of 1-3 microg/mL against wild-type E. coli.
Chen
M H
MH
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Steiner
M G
MG
de Laszlo
S E
SE
Patchett
A A
AA
Anderson
M S
MS
Hyland
S A
SA
Onishi
H R
HR
Silver
L L
LL
Raetz
C R
CR
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D008050:Lipid A / Q000096:biosynthesis*; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C101987:L 161240; C101988:L 573655; D008050:Lipid A; D010080:Oxazoles; D000581:Amidohydrolases; C097307:UDP-3-O-acyl-N-acetylglucosamine deacetylase