Discovery of Azaindole Ureas as a Novel Class of Bacterial Gyrase B Inhibitors

The emergence and spread of multidrug resistant bacteria are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the discovery of azaindole ureas as a novel class of bacterial gyrase B inhibitors and detail the story of their evolution from a <i>de novo</i> design hit based on structure-based drug design. These inhibitors show potent minimum inhibitory concentrations against fluoroquinolone resistant <i>MRSA</i> and other Gram-positive bacteria.