LEGER R, RENAU TE, ZHANG JZ, BELEJ P, FLAMME EM, MCMILLAN W, SANGALANG J, SHE MW, YEN R, CHAMBERLAND S, GANNON CL, LOMOVSKAYA O, LEE VJ; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 207.
Microcide Pharmaceuticals Inc., Mountain View, CA
In an accompanying abstract we described the identification of D-Orn-D-hPhe-3NHQ (1) as a stable, broad-spectrum efflux pump inhibitor (EPI) that potentiates the activity of levofloxacin in P. aeruginosa. Based on these results, 1 became the new lead in our campaign to evaluate the SAR of the EPIs. With this information we expanded our synthetic scope beyond the peptide backbone to include a variety of peptidomimetics, including tertiary amides, ethers, thioethers, hydroxymethylene groups and oxazoles. Overall we prepared a variety of peptidomimetics with diverse structure that potentiate the MIC of levofloxacin in P. aeruginosa 8-fold at concentrations of EPI that range from 0.625 to 20 microg/mL. The preparation and SAR of key compounds from this study are highlighted.KEYWORDS: Efflux pump inhibitors; Levofloxacin; Pseudomonas aeruginosa
Publication Types:
Keywords:
- Dipeptides
- Lactams
- Microbial Sensitivity Tests
- Ofloxacin
- Pseudomonas aeruginosa
- antagonists & inhibitors
- antibiotic PS 8
Other ID:
UI: 102247855
From Meeting Abstracts