Synthesis and antibacterial activity of the tricyclic ketolides TE-802 and its analogs.
The novel 6-O-methyl tricyclic ketolides TE-802 and its analogs were synthesized by two successive cyclization reactions, 11,12-cyclic carbamate formation by intramolecular Michael addition and 9,11-diazaheptene ring construction by intramolecular dehydration reaction. These new tricyclic ketolides exhibited good in vitro antibacterial activity against not only erythromycin-susceptible strains but also erythromycin-resistant Staphylococcus aureus and Streptococcus pneumoniae, which are problematic pathogens of nosocomial and community-acquired respiratory tract infections, respectively.
Kashimura
M
M
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan. m.kashimura@po.rd.taisho.co.jp
Asaka
T
T
Misawa
Y
Y
Matsumoto
K
K
Morimoto
S
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000494:pharmacology; D048628:Ketolides; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; C437368:TE-802; D004917:Erythromycin