Synthesis and antibacterial activity of C6-carbazate ketolides.
A novel series of ketolides containing heteroaryl groups that are linked to the erythronolide ring via a C6-carbazate functionality has been successfully synthesized. Careful modulation of the heteroaryl groups, the length and degree of saturation of the C6-carbazate linker, and the substituents present on each of the carbazate nitrogens led to compounds with potent activity against key bacterial respiratory pathogens. The best analogs of this series had in vitro and in vivo (sc dosing) profiles that were comparable to telithromycin.
Tennakoon
Manomi A
MA
Johnson & Johnson Pharmaceutical Research & Development, L.L.C, 1000 Route 202, PO Box 300, Raritan, NJ 08869, USA. mtennako@prdus.jnj.com
Henninger
Todd C
TC
Abbanat
Darren
D
Foleno
Barbara D
BD
Hilliard
Jamese J
JJ
Bush
Karen
K
Macielag
Mark J
MJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006834:Hydrazines; D048628:Ketolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013210:Staphylococcus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006834:Hydrazines; D048628:Ketolides; C010877:carbazic acid