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

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 Langgaard Kristensen

doi:10.1021/acs.jmedchem.5b00095

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

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 Langgaard Kristensen

19 Citationer (Scopus)

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 (11)C-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.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	58
Udgave nummer	8
Sider (fra-til)	3631–3636
Antal sider	16
ISSN	0022-2623
DOI	https://doi.org/10.1021/acs.jmedchem.5b00095
Status	Udgivet - 23 apr. 2015

Adgang til dokumentet

10.1021/acs.jmedchem.5b00095

Citationsformater

Herth, M. M., Andersen, V. L., Hansen, H. D., Stroth, N., Volk, B., Lehel, S., Dyssegaard, A., Ettrup, A., Svenningsson, P., Knudsen, G. M., & Kristensen, J. L. (2015). 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. Journal of Medicinal Chemistry, 58(8), 3631–3636. https://doi.org/10.1021/acs.jmedchem.5b00095

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. / Herth, Matthias M; Andersen, Valdemar L; Hansen, Hanne D et al.

I: Journal of Medicinal Chemistry, Bind 58, Nr. 8, 23.04.2015, s. 3631–3636.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Herth, MM, Andersen, VL, Hansen, HD, Stroth, N, Volk, B, Lehel, S, Dyssegaard, A, Ettrup, A, Svenningsson, P, Knudsen, GM & Kristensen, JL 2015, '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', Journal of Medicinal Chemistry, bind 58, nr. 8, s. 3631–3636. https://doi.org/10.1021/acs.jmedchem.5b00095

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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 (11)C-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.",

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AU - Herth, Matthias M

AU - Andersen, Valdemar L

AU - Hansen, Hanne D

AU - Stroth, Nikolas

AU - Volk, Balázs

AU - Lehel, Szabolcs

AU - Dyssegaard, Agnete

AU - Ettrup, Anders

AU - Svenningsson, Per

AU - Knudsen, Gitte M

AU - Kristensen, Jesper Langgaard

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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

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