Synthesis and structural–activity relationships of 3-hydroxyquinazoline-2,4-dione antibacterial agents

The synthesis and SAR of the 3-hydroxyquinazoline diones, a novel class of bacterial topoisomerase inhibitors, is reported. A series of 3-hydroxyquinazoline-2,4-diones was synthesized and evaluated for antibacterial activity. This series represents a novel addition to the DNA gyrase inhibitor class of antibacterials. Appropriate substitutions onto the core template yielded compounds with excellent potency against E. coli gyrase and significant in vitro Gram-negative and Gram-positive antibacterial activity.