National Center for
3G75: Crystal Structure Of Staphylococcus Aureus Gyrase B Co-complexed With 4-methyl-5-[3-(methylsulfanyl)-1h-pyrazol-5-yl]-2-thiophen-2-yl-1,3- Thiazole Inhibitor
Bioorg. Med. Chem. Lett. (2010) 20 p.2828-2831
Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphylococcus aureus GyrB.