Discovery of potent and selective adamantane-based small-molecule P2X(7) receptor antagonists/interleukin-1beta inhibitors

J Med Chem. 2007 Nov 29;50(24):5882-5. doi: 10.1021/jm700949w. Epub 2007 Oct 27.

Abstract

A novel series of antagonists of the human P2X7 receptor is described. Modification of substituents enabled identification of compounds selective for the rat P2X7 receptor and provides useful pharmacological tools for evaluation of the role of P2X7 in disease.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemical synthesis*
  • Adamantane / pharmacology
  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacology
  • Blood Proteins / metabolism
  • Crystallography, X-Ray
  • Humans
  • In Vitro Techniques
  • Interleukin-1beta / antagonists & inhibitors*
  • Molecular Conformation
  • Monocytes / metabolism
  • Protein Binding
  • Purinergic P2 Receptor Antagonists*
  • Rats
  • Receptors, Purinergic P2X7
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Blood Proteins
  • Interleukin-1beta
  • P2RX7 protein, human
  • P2rx7 protein, rat
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Adamantane