title: Synthesis and antibacterial activity of C6-carbazate ketolides.
abstract: 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.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C, 1000 Route 202, PO Box 300, Raritan, NJ 08869, USA. mtennako@prdus.jnj.com
authors.forename: Manomi A
authors.initials: MA
authors.lastname: Tennakoon
authors.forename: Todd C
authors.initials: TC
authors.lastname: Henninger
authors.forename: Darren
authors.initials: D
authors.lastname: Abbanat
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Foleno
authors.forename: Jamese J
authors.initials: JJ
authors.lastname: Hilliard
authors.forename: Karen
authors.initials: K
authors.lastname: Bush
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Macielag
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D006834:Hydrazines; D048628:Ketolides; C010877:carbazic acid