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.
Kaneko
Takushi
T
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. takushikaneko@gmail.com
Romero
Karina
K
Li
Bryan
B
Buzon
Richard
R
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D048628:Ketolides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D048628:Ketolides