Parallel synthesis of potent, pyrazole-based inhibitors of Helicobacter pylori dihydroorotate dehydrogenase

Article abstract of DOI:10.1021/jm020112w

The identification of several potent pyrazole-based inhibitors of bacterial dihydroorotate dehydrogenase (DHODase) via a directed parallel synthetic approach is described below. The initial pyrazole-containing lead compounds were optimized for potency against Helicobacter pylori DHODase. Using three successive focused libraries, inhibitors were rapidly identified with the following characteristics: K_i < 10 nM against H. pylori DHODase, sub-μg/mL H. pylori minimum inhibitory concentration activity, low molecular weight, and > 10 000-fold selectivity over human DHODase.