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

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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.

Highly selective dopamine D3 receptor radioligands were synthesized. The benzofuran derivative 11b displayed D3 selectivity of 560-fold over D2 (Ki 5.7 nM) justifying an application as a SPET radioligand.

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Acknowledgments

We thank Dr. J.-C. Schwartz and Dr. P. Sokoloff (INSERM, Paris), Dr. H. H. M. Van Tol (Clarke Institute of Psychiatry, Toronto), and Dr. J. Shine (The Garvan Institute of Medical Research, Sydney) for providing D3, D4.4, and D2 receptor expressing cell lines. Special thanks are due to Mrs. S. Pachaly, Mrs. H. Szczepanek, Mrs. P. Schmitt, and Mrs. P. Hübner for skillful technical assistance.

This work was supported by a grant from the ELAN-Fonds of the Friedrich-Alexander University Erlangen

References (16)

  • W.-M Owton

    Tetrahedron Lett.

    (2003)
    A.-J Bridges et al.

    Tetrahedron Lett.

    (1992)
  • V Asghari et al.

    J. Neurochem.

    (1995)
  • P Sokoloff et al.

    Nature

    (1990)
  • M Pilla et al.

    Nature

    (1999)
  • L Bettinetti et al.

    J. Med. Chem.

    (2002)
  • F Böckler et al.

    Biochem. Pharmacol.

    (2003)
  • O Prante et al.

    J. Labelled Compd. Radiopharm.

    (2001)
There are more references available in the full text version of this article.

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