Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor

Bioorg Med Chem Lett. 2010 May 15;20(10):3161-4. doi: 10.1016/j.bmcl.2010.03.096. Epub 2010 Mar 30.

Abstract

High-throughput screening identified compound 1 as a potent P2X(7) receptor antagonist suitable for lead optimisation. Structure-activity relationships (SAR) of a series of (1H-pyrazol-4-yl)acetamides were investigated and compound 32 was identified as a potent P2X(7) antagonist with enhanced potency and favourable physicochemical and pharmacokinetic properties.

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry*
  • Acetamides / pharmacokinetics
  • Administration, Oral
  • Animals
  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacokinetics
  • High-Throughput Screening Assays
  • Humans
  • Injections, Intravenous
  • Purinergic P2 Receptor Antagonists*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacokinetics
  • Rats
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2X7
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Anti-Infective Agents
  • P2RX7 protein, human
  • Purinergic P2 Receptor Antagonists
  • Pyrazoles
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7