Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against gram-positive pathogens.
Potent nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase have been derived from a file compound high throughput screening hit. Optimized compounds show excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics. Compound 11 demonstrated in vivo efficacy in an S. aureus rat abscess infection model.
Jarvest
Richard L
RL
Berge
John M
JM
Berry
Valerie
V
Boyd
Helen F
HF
Brown
Murray J
MJ
Elder
John S
JS
Forrest
Andrew K
AK
Fosberry
Andrew P
AP
Gentry
Daniel R
DR
Hibbs
Martin J
MJ
Jaworski
Deborah D
DD
O'Hanlon
Peter J
PJ
Pope
Andrew J
AJ
Rittenhouse
Stephen
S
Sheppard
Robert J
RJ
Slater-Radosti
Courtney
C
Worby
Angela
A
D000038:Abscess / Q000188:drug therapy / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D016983:Enterococcus / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013210:Staphylococcus / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D015363:Quinolones; D008718:Methionine-tRNA Ligase