Discovery and in vivo evaluation of alcohol-containing benzothiazoles as potent dual-targeting bacterial DNA supercoiling inhibitors

作者：Palmer James T^*; Axford Lorraine C; Barker Stephanie; Bennett James M; Blair Michael; Collins Ian; Davies David T; Ford Leigh; Gannon Carlie T; Lancett Paul; Logan Alastair; Lunniss Christopher J; Morton Craig J; Offermann Daniel A; Pitt Gary R W; Rao B Narasinga; Singh Amit K; Shukla Tarun; Srivastava Anil; Stokes Neil R; Thomaides Brears Helena B; Yadav Anju; Haydon David J

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(17): 4215-4222.

DOI：10.1016/j.bmcl.2014.07.037

• DNA gyrase
• Topoisomerase
• Antibacterial
• Synthesis
• In vivo
• Dual-targeting

A series of dual-targeting, alcohol-containing benzothiazoles has been identified with superior antibacterial activity and drug-like properties. Early lead benzothiazoles containing carboxylic acid moieties showed efficacy in a well-established in vivo model, but inferior drug-like properties demanded modifications of functionality capable of demonstrating superior efficacy. Eliminating the acid group in favor of hydrophilic alcohol moieties at C-5, as well as incorporating solubilizing groups at the C-7 position of the core ring provided potent, broad-spectrum Gram-positive antibacterial activity, lower protein binding, and markedly improved efficacy in vivo.

• 出版日期2014-9-1