Bioorganic & Medicinal Chemistry 2004-11-01

Synthesis and antibacterial activity of novel and potent DNA gyrase inhibitors with azole ring.

Akihiko Tanitame, Yoshihiro Oyamada, Keiko Ofuji, Mika Fujimoto, Kenji Suzuki, Tomohiko Ueda, Hideo Terauchi, Motoji Kawasaki, Kazuo Nagai, Masaaki Wachi, Jun-ichi Yamagishi

文献索引：Bioorg. Med. Chem. 12(21) , 5515-24, (2004)

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摘要

The 4-piperidyl moiety and the pyrazole ring in 1-(3-chlorophenyl)-5-(4-phenoxyphenyl)-3-(4-piperidyl)pyrazole 2, which has previously shown improved DNA gyrase inhibition and target-related antibacterial activity, were transformed to other groups and the in vitro antibacterial activity of the synthesized compounds was evaluated. The selected pyrazole, oxazole and imidazole derivatives showed moderate inhibition against DNA gyrase and topoisomerase IV with similar IC(50) values (IC(50)=9.4-25 microg/mL). In addition, many of the pyrazole, oxazole and imidazole derivatives synthesized in this study exhibited potent antibacterial activity against quinolone-resistant clinical isolates and coumarin-resistant laboratory isolates of Gram-positive bacteria with minimal inhibitory concentration values equivalent to those against susceptible strains.