Potent inhibitors of LpxC for the treatment of Gram-negative infections

J Med Chem. 2012 Jan 26;55(2):914-23. doi: 10.1021/jm2014748. Epub 2012 Jan 11.

Abstract

In this paper, we present the synthesis and SAR as well as selectivity, pharmacokinetic, and infection model data for representative analogues of a novel series of potent antibacterial LpxC inhibitors represented by hydroxamic acid.

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology
  • Catalytic Domain
  • Crystallography, X-Ray
  • Drug Resistance, Bacterial
  • Hydrogen Bonding
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Phenyl Ethers / chemical synthesis*
  • Phenyl Ethers / chemistry
  • Phenyl Ethers / pharmacology
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas aeruginosa
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfides / chemical synthesis*
  • Sulfides / chemistry
  • Sulfides / pharmacology
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry
  • Sulfones / pharmacology

Substances

  • Anti-Bacterial Agents
  • Biphenyl Compounds
  • Hydroxamic Acids
  • Phenyl Ethers
  • Sulfides
  • Sulfones
  • Amidohydrolases
  • LpxC deacetylase, Pseudomonas
  • UDP-3-O-acyl-N-acetylglucosamine deacetylase

Associated data

  • PDB/3U1Y