Discovery of a 4-aryloxy-1H-pyrrolo[3,2-c]pyridine and a 1-aryloxyisoquinoline series of TRPA1 antagonists

Bioorg Med Chem Lett. 2014 Jul 15;24(14):3199-203. doi: 10.1016/j.bmcl.2014.04.045. Epub 2014 Apr 19.

Abstract

A series of TRPA1 antagonists is described having a 4-aryloxy-1H-pyrrolo[3,2-c]pyridine or a 1-aryloxyisoquinoline scaffold. These compounds have high ligand efficiency and favorable physical properties and may thus serve as scaffolds for further optimization.

Keywords: Antagonist; Ligand gated ion channel; TRPA1.

MeSH terms

  • Calcium Channels
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Molecular Structure
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / antagonists & inhibitors*

Substances

  • Calcium Channels
  • Isoquinolines
  • Nerve Tissue Proteins
  • Pyridines
  • Pyrroles
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels