Inhibitors of bacterial tyrosyl tRNA synthetase: synthesis of carbocyclic analogues of the natural product SB-219383.
Carbocyclic analogues of the microbial metabolite SB-219383 have been synthesised and evaluated as inhibitors of bacterial tyrosyl tRNA synthetase. One compound showed highly potent and selective nanomolar inhibition.
Jarvest
R L
RL
GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK.
Berge
J M
JM
Houge-Frydrych
C S
CS
Mensah
L M
LM
O'Hanlon
P J
PJ
Pope
A J
AJ
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001671:Biochemistry / Q000379:methods; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000201:enzymology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005663:Furans; C410784:SB 219383; D014443:Tyrosine; D014448:Tyrosine-tRNA Ligase