Synthesis and characterization of the first inhibitor of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD)

Chem Commun (Camb). 2017 Nov 28;53(95):12814-12817. doi: 10.1039/c7cc07582k.

Abstract

N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Phospholipase D / antagonists & inhibitors*
  • Phospholipase D / metabolism
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Quinazolinones
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • 2,4-dioxo-N-(4-(4-pyridyl)phenyl)-1H-quinazoline-6-sulfonamide
  • Enzyme Inhibitors
  • Quinazolines
  • Quinazolinones
  • Small Molecule Libraries
  • Sulfonamides
  • Phospholipase D
  • NAPEPLD protein, human