Novel tethers in ketolide antibiotics

Novel macrolide antibiotics which contain a methylene unit between two nitrogen atoms of carbamate groups or between two nitrogen atoms of one carbamate 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.

Graphical abstractNovel tethers for ketolide analogues were developed using the Curtius rearrangement. The resulting compounds show potent in vitro and in vivo activity.Figure optionsDownload full-size imageDownload as PowerPoint slide