Synthesis and antibacterial activity of C2-fluoro, C6-carbamate ketolides, and their C9-oximes.
Xu X, Henninger T, Abbanat D, Bush K, Foleno B, Hilliard J, Macielag M.
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.