title: Synthesis and antibacterial activities of new quinolone derivatives utilizing 1-azabicyclo[1.1.0]butane.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ikee
authors.forename: Kana
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakashima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sano
authors.forename: Motoo
authors.initials: M
authors.lastname: Shiro
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nagao
mesh_terms: 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
chemical_list: C488447:1-azabicyclo(1,1,0)butane; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D007202:Indicators and Reagents; D015363:Quinolones