Synthesis and antibacterial properties of beta-diketone acrylate bioisosteres of pseudomonic acid A.
A series of beta-diketone acrylate bioisosteres 4 of pseudomonic acid A 1 have been synthesized and evaluated for their ability to inhibit bacterial isoleucyl-tRNA synthetase and act as antibacterial agents. A number of analogues have excellent antibacterial activity. Selected examples were shown to afford good blood levels and to be effective in a murine infection model.
Bennett
I
I
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Harlow, Essex, UK.
Broom
N J
NJ
Cassels
R
R
Elder
J S
JS
Masson
N D
ND
O'Hanlon
P J
PJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D007659:Ketones / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D016712:Mupirocin / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007659:Ketones; D016712:Mupirocin