Synthesis and antibacterial activity of C2-fluoro, C6-carbamate ketolides, and their C9-oximes.
Novel C6-carbamate ketolides with C2-fluorination and C9-oximation have been synthesized. The best compounds in this series displayed MIC values of 0.03-0.12 microg/mL against streptococci containing erm and mef resistance determinants and 2-4 microg/mL against Haemophilus influenzae. Several compounds also showed measurable activity against erm(B)-containing enterococci with MIC values of 2-8 microg/mL. In vivo activity was adversely affected by fluorination, possibly as a result of increased serum protein binding.
Xu
Xiaodong
X
Antimicrobial Agents Research Team, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 1000 Route 202, PO Box 300, Raritan, NJ 08869, USA. xxu@prdus.jnj.com
Henninger
Todd
T
Abbanat
Darren
D
Bush
Karen
K
Foleno
Barbara
B
Hilliard
Jamese
J
Macielag
Mark
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D048628:Ketolides / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D048628:Ketolides; D010091:Oximes