| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1378736 | Bioorganic & Medicinal Chemistry Letters | 2005 | 6 Pages |
A library of 4,5- and 4,6-linked bivalent aminoglycoside (AMG) antibiotics consisting of neamine and nebramine pharmacophores have been synthesized. We probed the effect of the linker on antibiotic activity with a series of selected synthetic analogues with varied length and substituents. A number of compounds demonstrated in vitro activity against several bacterial strains and showed activity against drug resistant strains of Pseudomonas aeruginosa. Among the compounds prepared, analogues 12a–d were novel 4,6-linked AMGs containing the nebramine pharmacophore. In addition the lead compound OPT-11 possessed an ED50 of ⩽5 mg/kg in a Staphylococcus aureus ATCC 29213 mouse protection model.
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