Side chain SAR of bicyclic beta-lactamase inhibitors (BLIs). 1. Discovery of a class C BLI for combination with imipinem

Bioorg Med Chem Lett. 2010 Feb 1;20(3):918-21. doi: 10.1016/j.bmcl.2009.12.069. Epub 2009 Dec 23.

Abstract

Bridged monobactam beta-lactamase inhibitors were prepared and evaluated as potential partners for combination with imipenem to overcome class C beta-lactamase mediated resistance. The (S)-azepine analog 2 was found to be effective in both in vitro and in vivo assays and was selected for preclinical development.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Carbapenems / chemistry*
  • Carbapenems / pharmacology
  • Drug Combinations
  • Drug Discovery / methods*
  • Imipenem / chemistry*
  • Imipenem / pharmacology
  • Mice
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / enzymology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / physiology
  • Structure-Activity Relationship
  • beta-Lactam Resistance / drug effects
  • beta-Lactam Resistance / physiology
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Carbapenems
  • Drug Combinations
  • beta-Lactamase Inhibitors
  • Imipenem
  • beta-Lactamases