Design, synthesis and biological evaluation of alpha-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors

作者：Axford Lorraine C^*; Agarwal Piyush K; Anderson Kelly H; Andrau Laura N; Atherall John; Barker Stephanie; Bennett James M; Blair Michael; Collins Ian; Czaplewski Lloyd G; Davies David T; Gannon Carlie T; Kumar Dushyant; Lancett Paul; Logan Alastair; Lunniss Christopher J; Mitchell Dale R; Offermann Daniel A; Palmer James T; Palmer Nicholas; Pitt Gary R W; Pommier Stephanie; Price Daniel; Rao B Narasinga; Saxena Rashmi; Shukla Tarun; Singh Amit K

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(24): 6598-6603.

DOI：10.1016/j.bmcl.2013.10.058

• DNA gyrase
• Topoisomerase
• Antibacterial

The discovery and optimisation of a new class of benzothiazole small molecules that inhibit bacterial DNA gyrase and topoisomerase IV are described. Antibacterial properties have been demonstrated by activity against DNA gyrase ATPase and potent activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Haemophilus influenzae. Further refinements to the scaffold designed to enhance drug-likeness included analogues bearing an alpha-substituent to the carboxylic acid group, resulting in excellent solubility and favourable pharmacokinetic properties.

• 出版日期2013-12-15