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Eur J Med Chem. 2014 May 22;79:152-63. doi: 10.1016/j.ejmech.2014.03.066. Epub 2014 Mar 29.

Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor.

Author information

  • 1Center for Integrated Molecular Brain Imaging, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
  • 2Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari A. Moro, Via Orabona, 4, 70125 Bari, Italy.
  • 3Center for Integrated Molecular Brain Imaging, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; PET and Cyclotron Unit, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
  • 4PET and Cyclotron Unit, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
  • 5Center for Integrated Molecular Brain Imaging, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: gmk@nru.dk.

Abstract

In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [(11)C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7 receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [(11)C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7 receptor PET radioligands.

Copyright © 2014 Elsevier Masson SAS. All rights reserved.

KEYWORDS:

5-HT(7) receptor; Arylpiperazine; PET; Radioligand; SB-269970

PMID:
24732791
[PubMed - indexed for MEDLINE]
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