Heteroarylureas with spirocyclic diamine cores as inhibitors of fatty acid amide hydrolase

Bioorg Med Chem Lett. 2014 Feb 1;24(3):737-41. doi: 10.1016/j.bmcl.2013.12.113. Epub 2014 Jan 6.

Abstract

A series of mechanism based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with spirocyclic diamine cores is described. A potent member of this class, (37), was found to inhibit FAAH centrally, elevate the brain levels of three fatty acid ethanolamides [FAAs: anandamide (AEA), oleoyl ethanolamide (OEA) and palmitoyl ethanolamide (PEA)], and was moderately efficacious in a rat model of neuropathic pain.

Keywords: Covalent inhibitor; FAAH; Hydrolase; Spirocycles.

MeSH terms

  • Administration, Oral
  • Amidohydrolases / antagonists & inhibitors*
  • Animals
  • Azetidines / chemistry*
  • Azetidines / pharmacokinetics
  • Azetidines / pharmacology*
  • Brain / enzymology
  • Brain / metabolism
  • Cyclization
  • Diamines / chemical synthesis*
  • Diamines / chemistry
  • Diamines / pharmacology
  • Enzyme Activation / drug effects
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology
  • Molecular Structure
  • Rats
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • Urea / analogs & derivatives*
  • Urea / chemistry
  • Urea / pharmacokinetics
  • Urea / pharmacology

Substances

  • Azetidines
  • Diamines
  • Heterocyclic Compounds
  • JNJ-42119779
  • Spiro Compounds
  • Urea
  • Amidohydrolases
  • fatty-acid amide hydrolase