title: Potent DNA gyrase inhibitors; novel 5-vinylpyrazole analogues with Gram-positive antibacterial activity.
abstract: In this study, we designed and synthesized novel 5-vinylpyrazole analogues by decreasing the lipophilicity of the parent compounds 1a,b; 3-[(3-methoxycarbonyl)cyclohexylaminomethyl]indazoles while keeping the van der Waals interaction with the lipophilic area of DNA gyrase B. The selected compound 8bb exhibited good antibacterial activity against staphylococci and enterococci, including multi-drug resistant strains.
authors.affiliation: Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd, 33-94, Enoki, Suita, Osaka 564-0053, Japan. akihiko-tanitame@dainiippon-pharm.co.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tanitame
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oyamada
authors.forename: Keiko
authors.initials: K
authors.lastname: Ofuji
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ito
authors.forename: Motoji
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Wachi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Yamagishi
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D013293:Enterococcus faecalis / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D040141:Staphylococcaceae / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D059005:Topoisomerase II Inhibitors