Structure-activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X(7) receptor

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4653-6. doi: 10.1016/j.bmcl.2010.05.107. Epub 2010 Jun 8.

Abstract

Structure-activity relationships (SAR) of analogues of lead compound 1 were investigated and compound 16 was selected for further study in animal models of pain. Compound 16 was shown to be a potent antihyperalgesic agent in both the rat acute complete Freund's adjuvant (CFA) model of inflammatory pain [Iadarola, M. J.; Douglass, J.; Civelli, O.; Naranjo, J. R. rain Res.1988, 455, 205] and the knee joint model of chronic inflammatory pain [Wilson, A. W.; Medhurst, S. J.; Dixon, C. I.; Bontoft, N. C.; Winyard, L. A.; Brackenborough, K. T.; De Alba, J.; Clarke, C. J.; Gunthorpe, M. J.; Hicks, G. A.; Bountra, C.; McQueen, D. S.; Chessell, I. P. Eur. J. Pain2006, 10, 537].

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry*
  • Acetamides / therapeutic use
  • Administration, Oral
  • Animals
  • Disease Models, Animal
  • Humans
  • Pain / drug therapy
  • Purinergic P2X Receptor Antagonists*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Rats
  • Receptors, Purinergic P2X7 / metabolism
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Purinergic P2X Receptor Antagonists
  • Pyrazoles
  • Receptors, Purinergic P2X7