Acylprolinamides: a new class of peptide deformylase inhibitors with in vivo antibacterial activity

Bioorg Med Chem Lett. 2012 Jun 15;22(12):4028-32. doi: 10.1016/j.bmcl.2012.04.086. Epub 2012 Apr 25.

Abstract

A new class of PDF inhibitor with potent, broad spectrum antibacterial activity is described. Optimization of blood stability and potency provided compounds with improved pharmacokinetics that were suitable for in vivo experiments. Compound 5c, which has robust antibacterial activity, demonstrated efficacy in two respiratory tract infection models.

MeSH terms

  • Administration, Oral
  • Amides / chemical synthesis*
  • Amides / pharmacology
  • Amidohydrolases / antagonists & inhibitors*
  • Amidohydrolases / metabolism
  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • Disease Models, Animal
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / growth & development
  • Humans
  • Injections, Intravenous
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis*
  • Proline / pharmacology
  • Rats
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / microbiology
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / growth & development
  • Structure-Activity Relationship

Substances

  • Amides
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Proline
  • Amidohydrolases
  • peptide deformylase