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 againstStaphylococcus 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 mu g mL(-1)(i.e.38 nM) to 2-4 mu g mL(-1)againstS. aureusATCC29213.