<p>Target-directed dynamic
combinatorial chemistry (tdDCC) enables the identification, as well as
optimization of ligands for un(der)explored targets such as the anti-infective
target 1‑deoxy‑d‑xylulose-5-phosphate synthase (DXS).
We report the unprecedented use of tdDCC to first identify and subsequently
optimize inhibitors of the anti-infective target DXS. Using tdDCC, we were able
to generate acylhydrazone-based inhibitors for DXS. The tailored tdDCC runs
also provided insights into the structure–activity relationship of this novel class
of DXS inhibitors. This approach holds the potential to expedite the drug
discovery process and could be generally applied to a range of biological
targets.</p>
Hit-Optimization Using Target-Directed Dynamic Combinatorial Chemistry: Development of Inhibitors of the Anti-Infective Target 1-Deoxy-D-Xylulose-5-Phosphate Synthase