Activity-directed expansion of a series of antibacterial agents.

The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL-1 (i.e. 38 nM) to 2-4 μg mL-1 against S. aureus ATCC29213.