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 de novo design hit based on structure-based
drug design. These inhibitors show potent minimum inhibitory concentrations
against fluoroquinolone resistant MRSA and other
Gram-positive bacteria.