Novel tethers in ketolide antibiotics

Novel macrolide antibiotics which contain a methylerie unit between two nitrogen atoms of carbarnate groups or between two nitrogen atoms of one carbarnate and one urea group were synthesized using the Curtius rearrangement. Such linkers were shown to be stable under physiological conditions, and the resulting ketolides show potent in vitro and in vivo activity against macrolide-resistant respiratory pathogens. The SAR of various heterocycles and linkers was established. (C) 2007 Elsevier Ltd. All rights reserved.