Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5‑HT7 Receptor Imaging with PET

• Published in: ACS chemical neuroscience Vol. 3; no. 12; pp. 1002 - 1007
• Main Authors: Herth, Matthias M, Volk, Balázs, Pallagi, Katalin, Kofoed Bech, Lasse, Antoni, Ferenc A, Knudsen, Gitte M, Kristensen, Jesper L
• Format: Journal Article
• Language: English
• Published: American Chemical Society 31.08.2012
• Subjects: Letter; Oxindole; 5-HT7 receptor distribution; PET
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/cn3001137

The most recently discovered serotonin (5-HT) receptor subtype, 5-HT7, is considered to be associated with several CNS disorders. Noninvasive in vivo positron emission tomography (PET) studies of cerebral 5-HT7 receptors could provide a significant advance in the understanding of the neurobiology and eventual dysfunctions of the 5-HT7 receptor. To date, no appropriate 5-HT7 receptor PET ligand has been developed. Here, we modified known 5-HT7 selective phenylpiperazinyl-butyloxindole derivatives so that they may be labeled either with carbon-11 or fluorine-18. A set of potential 5-HT7 ligands for PET molecular imaging was successfully synthesized. Two compounds (10 and 14) were tested against a range of targets. Both compounds display a promising in vitro profile with respect to PET imaging of the 5-HT7 receptor in thalamic regions.