Synthesis and radioiodination of selective ligands for the dopamine D3 receptor subtype

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3963-6. doi: 10.1016/j.bmcl.2004.05.052.

Abstract

Starting from FAUC 365, a series of iodine substituted heteroaryl carboxamides has been synthesized revealing high affinity and selectivity for the dopamine D3 receptor. Binding data showed a 15-560-fold selectivity for the dopamine D3 over D2. A 2,3-dichloro substitution pattern on the phenylpiperazine moiety led to the highest subtype selectivity, whereas the 2-methoxy substituted compounds showed superior D3 affinity. Suitable precursors were radioiodinated with high radiochemical yields (53-85%) leading to potential imaging agents for the D3 receptor by SPET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dopamine D2 Receptor Antagonists
  • Indicators and Reagents
  • Iodine Radioisotopes
  • Kinetics
  • Ligands
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3
  • Thiophenes / chemistry
  • Thiophenes / pharmacology

Substances

  • Dopamine D2 Receptor Antagonists
  • FAUC 365
  • Indicators and Reagents
  • Iodine Radioisotopes
  • Ligands
  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Thiophenes