Physical Sciences and Mathematics Commons^™

Structure-Activity Relationships Of 2-Aryl-1h-Indole Inhibitors Of The Nora Efflux Pump In Staphylococcus Aureus, John Bremner, Michael Kelso, Joseph Ambrus, Kim Lewis, Anthony Ball, Gabriele Casadei

Kim Lewis

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 Staphylococcus 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.