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

Matthias Manfred Herth; Balázs Volk; Katalin Pallagi; Lasse Koefoed Bech; Ferenc A. Antoni; Gitte Moos Knudsen; Jesper Langgaard Kristensen

doi:10.1021/cn3001137

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

Matthias Manfred Herth, Balázs Volk, Katalin Pallagi, Lasse Koefoed Bech, Ferenc A. Antoni, Gitte Moos Knudsen, Jesper Langgaard Kristensen

20 Citations (Scopus)

Abstract

The most recently discovered serotonin (5-HT) receptor subtype, 5-HT ₇, 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-HT ₇ 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.

Original language	English
Journal	ACS Chemical Neuroscience
Volume	3
Issue number	12
Pages (from-to)	1002-1007
ISSN	1948-7193
DOIs	https://doi.org/10.1021/cn3001137
Publication status	Published - 19 Dec 2012

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title = "Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET",

abstract = "The most recently discovered serotonin (5-HT) receptor subtype, 5-HT 7, 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-HT 7 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.",

author = "Herth, {Matthias Manfred} and Bal{\'a}zs Volk and Katalin Pallagi and {Koefoed Bech}, Lasse and {A. Antoni}, Ferenc and Knudsen, {Gitte Moos} and Kristensen, {Jesper Langgaard}",

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T1 - Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET

AU - Herth, Matthias Manfred

AU - Volk, Balázs

AU - Pallagi, Katalin

AU - Koefoed Bech, Lasse

AU - A. Antoni, Ferenc

AU - Knudsen, Gitte Moos

AU - Kristensen, Jesper Langgaard

PY - 2012/12/19

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AB - The most recently discovered serotonin (5-HT) receptor subtype, 5-HT 7, 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-HT 7 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.

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DO - 10.1021/cn3001137

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

Abstract

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