2-Substituted 4,5-dihydrothiazole-4-carboxylic acids are novel inhibitors of metallo-β-lactamases

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6229-32. doi: 10.1016/j.bmcl.2012.08.012. Epub 2012 Aug 10.

Abstract

Bacterial resistance to β-lactam antibiotics caused by class B metallo-β-lactamases (MBL), especially for certain hospital-acquired, Gram-negative pathogens, poses a significant threat to public health. We report several 2-substituted 4,5-dihydrothiazole-4-carboxylic acids to be novel MBL inhibitors. Structure activity relationship (SAR) and molecular modeling studies were performed and implications for further inhibitor design are discussed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • 4,5-dihydrothiazole-4-carboxylic acid
  • Carboxylic Acids
  • Enzyme Inhibitors
  • Thiazoles
  • beta-Lactamase Inhibitors
  • beta-Lactamases