VO NH, NIU D, HOU Y, WANG G, XU G, POLEMEROPOULOS A, AMSLER K, PHAN LT, OR YS; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. F-1195.
Enanta Pharmaceuticals Inc., Watertown, MA.
BACKGROUND: The recent discovery of a novel ketolide core (EP-1304), possessing good antibacterial properties, has opened up a number of opportunities for structure activity studies. To this end, oxime formation, derived from the 6,11-bridged alkene, was shown to be an effective synthetic tool for the introduction of secondary moieties to overcome MLS[B]-resistance. Preliminary studies indicated that the geometry of the oxime bridge is critical for broad antibacterial activity. Isoxazoles as part of the biaryl secondary binder provide high E/Z selectivity for the bridged oxime formation step. METHODS: Minimal inhibitory concentrations (MIC) were determined ultilizing the broth-microdilution method as per NCCLS standards. RESULTS: Typical MICs are in the range of: 0.13-0.50 microg/mL for S. aureus, Ery-S and for S. pneumoniae Ery-R-mef; 0.13-1.0 microg/mL for S. pyogenes, Ery-R-mef; and 2.0-64 microg/mL for S. pyogenes, Ery-R-erm as compared to 0.5, 8, 16, and >64 microg/mL respectively for erythromycin. [figure: see text] CONCLUSIONS: The aryl-isoxazoles-6,11-bridged oxime ketolides are active against a broad spectrum of pathogens including resistant strains.
Publication Types:
Keywords:
- Anti-Bacterial Agents
- Erythromycin
- Isoxazoles
- Ketolides
- Macrolides
- Microbial Sensitivity Tests
- Oximes
Other ID:
UI: 102265476
From Meeting Abstracts