Arylboronic acids as dual-action FAAH and TRPV1 ligands

Bioorg Med Chem Lett. 2016 Mar 1;26(5):1401-5. doi: 10.1016/j.bmcl.2016.01.071. Epub 2016 Jan 25.

Abstract

A series of 31 arylboronic acids designed on the basis of the pharmacophore model for a variety of TRPV1 antagonists was prepared and tested on FAAH and TRPV1 channel. Four of them, that is, compounds 3c, 4a, 5a,b acted as dual FAAH/TRPV1 blockers with IC50 values between 0.56 and 8.11μM whereas ten others (compounds 1c,f-i, 2c-f, 4b) inhibited FAAH and activated/desensitized TRPV1.

Keywords: Boronic acids; Dual-ligands; FAAH; Fatty acid amide hydrolase; TRPV1; Transient receptor potential vanilloid type-1 channel.

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Amidohydrolases / metabolism
  • Boronic Acids / chemical synthesis
  • Boronic Acids / chemistry
  • Boronic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Molecular Structure
  • Structure-Activity Relationship
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / metabolism

Substances

  • Boronic Acids
  • Enzyme Inhibitors
  • Ligands
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Amidohydrolases
  • fatty-acid amide hydrolase