Design, synthesis and biological evaluation of 伪-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors
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- 作者：Lorraine C. Axford ; Piyush K. Agarwal ; Kelly H. Anderson ; Laura N. Andrau ; John Atherall ; Stephanie Barker ; James M. Bennett ; Michael Blair ; Ian Collins ; Lloyd G. Czaplewski ; David T. Davies ; Carlie T. Gannon ; Dushyant Kumar ; Paul Lancett ; Alastair Logan ; Christopher J. Lunniss ; Dale R. Mitchell ; Daniel A. Offermann ; James T. Palmer ; Nicholas Palmer ; et al.
- 关键词：DNA gyrase ; Topoisomerase ; Antibacterial
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：15 December, 2013
- 年：2013
- 卷：23
- 期：24
- 页码：6598-6603
- 全文大小：1179 K
文摘
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 伪-substituent to the carboxylic acid group, resulting in excellent solubility and favourable pharmacokinetic properties.