Synthesis and in vitro evaluation of oxindole derivatives as potential radioligands for 5-HT(7) receptor imaging with PET

Matthias M Herth; Balázs Volk; Katalin Pallagi; Lasse Kofoed Bech; Ferenc A Antoni; Gitte M Knudsen; Jesper Langgaard Kristensen

doi:10.1021/cn3001137

Synthesis and in vitro evaluation of oxindole derivatives as potential radioligands for 5-HT(7) receptor imaging with PET

Matthias M Herth
, Balázs Volk
, Katalin Pallagi
, Lasse Kofoed Bech
, Ferenc A Antoni
, Gitte M Knudsen
, Jesper Langgaard Kristensen

Department of Neurology

27 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-HT(7) 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-HT(7) receptor PET ligand has been developed. Here, we modified known 5-HT(7) selective phenylpiperazinyl-butyloxindole derivatives so that they may be labeled either with carbon-11 or fluorine-18. A set of potential 5-HT(7) 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-HT(7) receptor in thalamic regions.

Original language	English
Journal	A C S Chemical Neuroscience
Volume	3
Issue number	12
Pages (from-to)	1002-7
Number of pages	6
ISSN	1948-7193
DOIs	https://doi.org/10.1021/cn3001137
Publication status	Published - 2012

Access to Document

10.1021/cn3001137

Cite this

@article{54e645c46991479e9727c5a51e555922,

title = "Synthesis and in vitro evaluation of oxindole derivatives as potential radioligands for 5-HT(7) 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-HT(7) 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-HT(7) receptor PET ligand has been developed. Here, we modified known 5-HT(7) selective phenylpiperazinyl-butyloxindole derivatives so that they may be labeled either with carbon-11 or fluorine-18. A set of potential 5-HT(7) 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-HT(7) receptor in thalamic regions.",

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

year = "2012",

doi = "10.1021/cn3001137",

language = "English",

volume = "3",

pages = "1002--7",

journal = "A C S Chemical Neuroscience",

issn = "1948-7193",

publisher = "American Chemical Society",

number = "12",

}

TY - JOUR

T1 - Synthesis and in vitro evaluation of oxindole derivatives as potential radioligands for 5-HT(7) receptor imaging with PET

AU - Herth, Matthias M

AU - Volk, Balázs

AU - Pallagi, Katalin

AU - Kofoed Bech, Lasse

AU - Antoni, Ferenc A

AU - Knudsen, Gitte M

AU - Kristensen, Jesper Langgaard

PY - 2012

Y1 - 2012

N2 - 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-HT(7) 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-HT(7) receptor PET ligand has been developed. Here, we modified known 5-HT(7) selective phenylpiperazinyl-butyloxindole derivatives so that they may be labeled either with carbon-11 or fluorine-18. A set of potential 5-HT(7) 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-HT(7) receptor in thalamic regions.

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-HT(7) 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-HT(7) receptor PET ligand has been developed. Here, we modified known 5-HT(7) selective phenylpiperazinyl-butyloxindole derivatives so that they may be labeled either with carbon-11 or fluorine-18. A set of potential 5-HT(7) 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-HT(7) receptor in thalamic regions.

U2 - 10.1021/cn3001137

DO - 10.1021/cn3001137

M3 - Journal article

C2 - 23259035

SN - 1948-7193

VL - 3

SP - 1002

EP - 1007

JO - A C S Chemical Neuroscience

JF - A C S Chemical Neuroscience

IS - 12

ER -

Synthesis and in vitro evaluation of oxindole derivatives as potential radioligands for 5-HT(7) receptor imaging with PET

Abstract

Access to Document

Fingerprint

Cite this