Structure–Activity Relationships of 2-Aryl-1H-indole Inhibitors of the NorA Efflux Pump in Staphylococcus aureus

摘要

The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh- mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on these indoles and 2-phenyl-1H-indole in S. aureus as NorA efflux pump inhibitors indicated 5-nitro-2-(3-methoxycarbonyl)phenyl-1H-indole was a slightly more potent inhibitor than the lead INF55. A promising new antibacterial lead compound against S. aureus, (2-phenyl-1H-indol-5-yl)-methanol, was also found.