Discovery of P2X3 selective antagonists for the treatment of chronic pain

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2565-71. doi: 10.1016/j.bmcl.2012.01.124. Epub 2012 Feb 9.

Abstract

Purinergic receptor P2X3 has been linked to analgesia in a number of pre-clinical models of pain, and is expressed in the human pain perception pathway. Only few P2X3-selective antagonists have been reported to date. This Letter describes the SAR and in vivo analgesic profile of a novel scaffold of selective P2X3 antagonists.

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / chemical synthesis*
  • Analgesics / therapeutic use
  • Animals
  • Chronic Pain / drug therapy*
  • Chronic Pain / metabolism
  • Dose-Response Relationship, Drug
  • High-Throughput Screening Assays
  • Humans
  • Injections, Spinal
  • Injections, Subcutaneous
  • Purinergic P2 Receptor Antagonists / administration & dosage
  • Purinergic P2 Receptor Antagonists / chemical synthesis*
  • Purinergic P2 Receptor Antagonists / therapeutic use
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / therapeutic use
  • Pyrroles / administration & dosage
  • Pyrroles / chemical synthesis*
  • Pyrroles / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X3 / chemistry*
  • Receptors, Purinergic P2X3 / metabolism
  • Small Molecule Libraries

Substances

  • Analgesics
  • Purinergic P2 Receptor Antagonists
  • Pyrimidinones
  • Pyrroles
  • Receptors, Purinergic P2X3
  • Small Molecule Libraries