Synthesis and activity of analogues of SB-219383: novel potent inhibitors of bacterial tyrosyl tRNA synthetase.
SB-219383 is a naturally occurring antibiotic, which acts by inhibition of tyrosyl tRNA synthetase. Semi-synthetic derivatives of SB-219383 were prepared with the objective of elucidating the key features required for inhibition of tyrosyl tRNA synthetase in order to improve the antibacterial activity. Some ester and amide derivatives as well as monocyclic analogues exhibited sub-nanomolar inhibitory activity against tyrosyl tRNA synthetase.
Berge
J M
JM
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
Broom
N J
NJ
Houge-Frydrych
C S
CS
Jarvest
R L
RL
Mensah
L
L
McNair
D J
DJ
O'Hanlon
P J
PJ
Pope
A J
AJ
Rittenhouse
S
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000201:enzymology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005663:Furans; C410784:SB 219383; D014448:Tyrosine-tRNA Ligase