Synthesis and activity of 2-[4-(4-[3H]-2-cyanophenyl)piperazinyl]-N-(2,4,6-[3H]3-3-methylphenyl)acetamide: a selective dopamine D4 receptor agonist and radioligand

Bioorg Med Chem Lett. 2004 Oct 18;14(20):5095-8. doi: 10.1016/j.bmcl.2004.07.068.

Abstract

The first selective dopamine D4 agonist radioligand is described. The synthesis of these piperazine radioligands relied on the transformation of brominated precursors 4a and 4b with tritium gas in the presence of a sensitive cyano functional group. The specific activity of these two radioligands was measured and [3H]6b found to be suitable for use in D4 saturation and competition binding studies. The synthesis, biological, and radioactivity of this new agonist radioligand as well as preliminary SAR will be discussed.

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / chemistry
  • Acetamides / pharmacology
  • Cell Line
  • Humans
  • In Vitro Techniques
  • Ligands
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Radioligand Assay
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D4
  • Structure-Activity Relationship
  • Tritium

Substances

  • Acetamides
  • DRD4 protein, human
  • Ligands
  • Piperazines
  • Receptors, Dopamine D2
  • Tritium
  • Receptors, Dopamine D4