Design, synthesis and evaluation of polar head group containing 2-keto-oxazole inhibitors of FAAH

Bioorg Med Chem. 2012 Jan 15;20(2):1100-12. doi: 10.1016/j.bmc.2011.11.027. Epub 2011 Nov 28.

Abstract

2-α-Keto oxazoles containing polar head groups in their C5-side chains were designed as fatty acid amide hydrolase (FAAH) inhibitors. Variation in the spacer length resulted in submicromolar α-keto-oxazole FAAH inhibitor (IC(50)=436 nM) presenting electrostatic stabilizing interactions between its polar head group contained in the C5-side chain and the hydrophilic pocket of the enzyme.

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Amidohydrolases / metabolism
  • Animals
  • Binding Sites
  • Computer Simulation
  • Drug Design*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Female
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry*
  • Oxazoles / pharmacology*
  • Protein Structure, Tertiary
  • Rats
  • Rats, Sprague-Dawley
  • Static Electricity

Substances

  • Enzyme Inhibitors
  • Oxazoles
  • Amidohydrolases
  • fatty-acid amide hydrolase