Palmer J.T.,Biota Scientific Management |
Axford L.C.,Biota Scientific Management |
Barker S.,Biota Europe Ltd |
Bennett J.M.,Biota Europe Ltd |
And 19 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2014
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 C7 position of the core ring provided potent, broad-spectrum Gram-positive antibacterial activity, lower protein binding, and markedly improved efficacy in vivo. © 2014 Elsevier Ltd. All rights reserved.