Side chain SAR of bicyclic β-lactamase inhibitors (BLIs). 2. N-Alkylated and open chain analogs of MK-8712

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4267-70. doi: 10.1016/j.bmcl.2011.05.065. Epub 2011 May 27.

Abstract

The bridged monobactam β-lactamase inhibitor MK-8712 (1) effectively inhibits class C β-lactamases. Side chain N-alkylated and ring-opened analogs of 1 were prepared and evaluated for combination with imipenem to overcome class C β-lactamase mediated resistance. Although some analogs were more potent inhibitors of AmpC, none exhibited better synergy with imipenem than 1.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Binding Sites
  • Computer Simulation
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Imipenem / pharmacology
  • Microbial Sensitivity Tests
  • Monobactams / chemical synthesis*
  • Monobactams / pharmacology
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • MK 8712
  • Monobactams
  • beta-Lactamase Inhibitors
  • Imipenem
  • beta-Lactamases