α-Aryl pyrrolidine sulfonamides as TRPA1 antagonists

Bioorg Med Chem Lett. 2016 Jan 15;26(2):495-498. doi: 10.1016/j.bmcl.2015.11.088. Epub 2015 Nov 25.

Abstract

A series of α-aryl pyrrolidine sulfonamide TRPA1 antagonists were advanced from an HTS hit to compounds that were stable in liver microsomes with retention of TRPA1 potency. Metabolite identification studies and physicochemical properties were utilized as a strategy for compound design. These compounds serve as starting points for further compound optimization.

Keywords: Ion channel; Metabolic stability; TRPA1.

MeSH terms

  • Animals
  • Calcium Channels
  • Humans
  • Microsomes, Liver / metabolism
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / pharmacology*
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / pharmacology*
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / antagonists & inhibitors*

Substances

  • Calcium Channels
  • Nerve Tissue Proteins
  • Pyrrolidines
  • Sulfonamides
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels