Synthesis and antibacterial activities of new quinolone derivatives utilizing 1-azabicyclo[1.1.0]butane.
The ring-opening reactions of 1-azabicyclo[1.1.0]butane 3 with thiols 6a-f gave 3-sulfenylazetidine derivatives 7a-f in 50-92% yields. Treatment of 3 with aromatic amines 11a-e and dibenzylamine 11f in the presence of Mg(ClO(4))(2) afforded the corresponding 3-aminoazetidine derivatives 12a-f in 24-53% yields. These azetidine derivatives were introduced into the C7 position of a quinolone nucleus 8 to afford the corresponding fluoroquinolones 9a-f and 13a-f in 21-83% yields. Some of them exhibited superior antibacterial activity against quinolone-susceptible MRSA in comparison with clinically used fluoroquinolones, such as levofloxacin, ciprofloxacin, and gatifloxacin.
Ikee
Yoshifumi
Y
Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan.
Hashimoto
Kana
K
Nakashima
Masaaki
M
Hayashi
Kazuhiko
K
Sano
Shigeki
S
Shiro
Motoo
M
Nagao
Yoshimitsu
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001372:Aza Compounds / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
C488447:1-azabicyclo(1,1,0)butane; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D007202:Indicators and Reagents; D015363:Quinolones