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

Abstract

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