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 μg/mL against streptococci containing erm and mef resistance determinants and 2–4 μg/mL against Haemophilus influenzae. Several compounds also showed measurable activity against erm(B)-containing enterococci with MIC values of 2–8 μg/mL. In vivo activity was adversely affected by fluorination, possibly as a result of increased serum protein binding.