Tetrahydro-β-carboline derivatives targeting fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channels

Bioorg Med Chem Lett. 2013 Jan 1;23(1):138-42. doi: 10.1016/j.bmcl.2012.10.137. Epub 2012 Nov 12.

Abstract

A series of twenty-five derivatives of tetrahydro-β-carbolines 1-3 was synthesized and assayed on FAAH and TRPV1 and TRPA1 channels. Four carbamates, that is, 5a,c,e, and 9b inhibited FAAH with significant potency and interacted also effectively with TRPV1 and TRPA1 nociceptive receptors, while ureas 7b,d,f, and 8a,b were endowed with specific submicromolar TRPV1 modulating activities.

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Amidohydrolases / metabolism
  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / metabolism
  • Calcium Channels / metabolism
  • Carbamates / chemistry
  • Carbolines / chemical synthesis
  • Carbolines / chemistry*
  • Carbolines / metabolism
  • Humans
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism
  • Protein Binding
  • Structure-Activity Relationship
  • TRPA1 Cation Channel
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels / antagonists & inhibitors*
  • Transient Receptor Potential Channels / metabolism
  • Urea / chemistry

Substances

  • Analgesics
  • Calcium Channels
  • Carbamates
  • Carbolines
  • Nerve Tissue Proteins
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels
  • Urea
  • Amidohydrolases
  • fatty-acid amide hydrolase