Structure–activity relationships of 3-aminoquinazolinediones, a new class of bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors

A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC50 =  0.2 μM) and activity against Gram-positive organisms (MIC’s  =  0.015–0.06 μ g/mL).

Graphical abstractThe syntheses and antibacterial SAR of the 3-aminoquinazolinediones are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide