jm5b00095_si_001.pdf (13.43 MB)

Evaluation of 3‑Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5‑HT7 Receptor: Synthesis, Pharmacology, Radiolabeling, and in Vivo Brain Imaging in Pigs

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journal contribution
posted on 23.04.2015, 00:00 by Matthias M. Herth, Valdemar L. Andersen, Hanne D. Hansen, Nikolas Stroth, Balázs Volk, Szabolcs Lehel, Agnete Dyssegaard, Anders Ettrup, Per Svenningsson, Gitte M. Knudsen, Jesper L. Kristensen
We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent 11C-labeling and in vivo evaluation in Danish landrace pigs showed that both ligands displayed high brain uptake. However, neither of the radioligands could be displaced by the 5-HT7 receptor selective inverse agonist SB-269970.