Publication

Synthesis and Characterization of a Novel Series of Agonist Compounds as Potential Radiopharmaceuticals for Imaging Dopamine D-2/3 Receptors in Their High-Affinity State

van Wieringen, J-P., Shalgunov, V., Janssen, H. M., Fransen, P. M., Janssen, A. G. M., Michel, M. C., Booij, J. & Elsinga, P. H., 23-Jan-2014, In : Journal of Medicinal Chemistry. 57, 2, p. 391-410 20 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Synthesis and Characterization of a Novel Series of Agonist Compounds

    Final publisher's version, 906 KB, PDF document

    Request copy

DOI

  • Jan-Peter van Wieringen
  • Vladimir Shalgunov
  • Henk M. Janssen
  • P. Michel Fransen
  • Anton G. M. Janssen
  • Martin C. Michel
  • Jan Booij
  • Philip H. Elsinga

Imaging of dopamine D-2/3 receptors (D2/3R) can shed light on the nature of several neuropsychiatric disorders in which dysregulation of D2/3R signaling is involved. Agonist D-2/3 tracers for PET/SPECT imaging are considered to be superior to antagonists because they are more sensitive to dopamine concentrations and may selectively label the high-affinity receptor state. Carbon-11-labeled D2/3R agonists have been developed, but these short-lived tracers can be used only in centers with a cyclotron. Here, we report the development of a series of novel D2R agonist compounds based on the 2-aminomethylchromane (AMC) scaffold that provides ample opportunities for the introduction of longer-lived [F-18] or [I-123]. Binding experiments showed that several AMC compounds have a high affinity and selectivity for D2/3R and act as agonists. Two fluorine-containing compounds were [18(F)]-labeled, and both displayed specific binding to striatal D2/3R in rat brain slices in vitro. These findings encourage further in vivo evaluations.

Original languageEnglish
Pages (from-to)391-410
Number of pages20
JournalJournal of Medicinal Chemistry
Volume57
Issue number2
Publication statusPublished - 23-Jan-2014

    Keywords

  • POSITRON-EMISSION-TOMOGRAPHY, IN-VIVO ACTIVITY, D-3 RECEPTOR, HUMAN BRAIN, ENDOGENOUS DOPAMINE, ANTERIOR-PITUITARY, LIGAND-BINDING, AGENTS, DERIVATIVES, PHARMACOPHORE

ID: 16168859