Potent synthetic inhibitors of tyrosyl tRNA synthetase derived from C-pyranosyl analogues of SB-219383.
Novel pyranosyl analogues of SB-219383 have been synthesised to elucidate the structure-activity relationships around the pyran ring. Analogues with highly potent stereoselective and bacterioselective inhibition of bacterial tyrosyl tRNA synthetase have been identified. A major reduction in the overall polarity of the molecule can be tolerated without loss of the nanomolar level of inhibition.
Jarvest
R L
RL
GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. pam_brown-1@sbphrd.com
Berge
J M
JM
Brown
P
P
Hamprecht
D W
DW
McNair
D J
DJ
Mensah
L
L
O'Hanlon
P J
PJ
Pope
A J
AJ
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D011714:Pyrans / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000378:metabolism; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors*
D001426:Bacterial Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005663:Furans; D011714:Pyrans; C410784:SB 219383; D014448:Tyrosine-tRNA Ligase