The chemistry of pseudomonic acid. Part 14. Synthesis and in vivo biological activity of heterocyclyl substituted oxazole derivatives.
Semisynthetic analogues of pseudomonic acid A have been prepared containing a heterocyclyl substituted oxazole. Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo. Both pharmacokinetic parameters and oral activity against an experimental intraperitoneal sepsis were superior to results obtained from previously described pseudomonic acid A derivatives.
Broom
N J
NJ
SmithKline Beecham Pharmaceuticals, Brockham Park, Betchworth, Surrey.
Elder
J S
JS
Hannan
P C
PC
Pons
J E
JE
O'Hanlon
P J
PJ
Walker
G
G
Wilson
J
J
Woodall
P
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005663:Furans / Q000138:chemical synthesis; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis; D051379:Mice; D016712:Mupirocin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000627:therapeutic use; D010080:Oxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011720:Pyrazoles / Q000138:chemical synthesis; D011725:Pyridines / Q000138:chemical synthesis; D018805:Sepsis / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy; D013844:Thiazoles / Q000138:chemical synthesis; D013876:Thiophenes / Q000138:chemical synthesis
D000900:Anti-Bacterial Agents; D005663:Furans; D007555:Isoxazoles; D010080:Oxazoles; D011720:Pyrazoles; D011725:Pyridines; D013844:Thiazoles; D013876:Thiophenes; D016712:Mupirocin