Synthesis and antibacterial activity of a novel series of potent DNA gyrase inhibitors. Pyrazole derivatives.
We have previously found that a pyrazole derivative 1 possesses antibacterial activity and inhibitory activity against DNA gyrase and topoisomerase IV. Here, we synthesized new pyrazole derivatives and found that 5-[(E)-2-(5-chloroindol-3-yl)vinyl]pyrazole 16 possesses potent antibacterial activity and selective inhibitory activity against bacterial topoisomerases. Many of the synthesized pyrazole derivatives were potent against clinically isolated quinolone- or coumarin-resistant Gram-positive strains and had minimal inhibitory concentration values against these strains equivalent to those against susceptible strains.
Tanitame
Akihiko
A
Chemistry Research Laboratories, Pharmacology and Microbiology Research Laboratories, Dainippon Pharmaceutical Co. Ltd., 33-94 Enoki, Suita, Osaka 564-0053, Japan. akihiko-tanitame@dainippon-pharm.co.jp
Oyamada
Yoshihiro
Y
Ofuji
Keiko
K
Fujimoto
Mika
M
Iwai
Noritaka
N
Hiyama
Yoichi
Y
Suzuki
Kenji
K
Ito
Hideaki
H
Terauchi
Hideo
H
Kawasaki
Motoji
M
Nagai
Kazuo
K
Wachi
Masaaki
M
Yamagishi
Jun-ichi
J
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
C488120:5-(2-(5-chloroindol-3-yl)vinyl)pyrazole; D000900:Anti-Bacterial Agents; D007211:Indoles; D011720:Pyrazoles; D059005:Topoisomerase II Inhibitors; D027101:DNA Topoisomerase IV