Synthesis and functional activity of (2-aryl-1-piperazinyl)-N-(3-methylphenyl)acetamides: selective dopamine D4 receptor agonists

Bioorg Med Chem. 2004 Jul 1;12(13):3471-83. doi: 10.1016/j.bmc.2004.04.035.


Diaryl piperazine acetamides were identified as potent and selective dopamine D(4) receptor agonists. Our strategy is based on an amide bond reversal of an acid sensitive, dopamine D(4) receptor partial agonist, PD 168077. This reversal provided compounds with excellent potency and improved stability. Systematic evaluation of the substitution on the aryl piperazine portion revealed a significant effect on functional activity. The synthesis and biological activity of these new dopamine D(4) agonists is discussed.

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry*
  • Acetamides / pharmacology*
  • Calcium / metabolism
  • Cell Line
  • Dopamine Agonists / chemical synthesis*
  • Dopamine Agonists / chemistry
  • Dopamine Agonists / pharmacology*
  • Humans
  • Molecular Structure
  • Radioligand Assay
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D4


  • Acetamides
  • DRD4 protein, human
  • Dopamine Agonists
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Calcium