Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor

Hanne D Hansen; Enza Lacivita; Pantaleo Di Pilato; Matthias M Herth; Szabolcs Lehel; Anders Ettrup; Valdemar Lykke Andersen; Agnete Dyssegaard; Paola De Giorgio; Roberto Perrone; Francesco Berardi; Nicola Antonio Colabufo; Mauro Niso; Gitte M Knudsen; Marcello Leopoldo

doi:10.1016/j.ejmech.2014.03.066

Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor

Hanne D Hansen, Enza Lacivita, Pantaleo Di Pilato, Matthias M Herth, Szabolcs Lehel, Anders Ettrup, Valdemar Lykke Andersen, Agnete Dyssegaard, Paola De Giorgio, Roberto Perrone, Francesco Berardi, Nicola Antonio Colabufo, Mauro Niso, Gitte M Knudsen, Marcello Leopoldo

25 Citationer (Scopus)

Abstract

In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [(11)C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7 receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [(11)C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7 receptor PET radioligands.

Originalsprog	Engelsk
Tidsskrift	European Journal of Medicinal Chemistry
Vol/bind	79
Sider (fra-til)	152-63
Antal sider	12
ISSN	0223-5234
DOI	https://doi.org/10.1016/j.ejmech.2014.03.066
Status	Udgivet - 22 maj 2014

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10.1016/j.ejmech.2014.03.066

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Hansen, H. D., Lacivita, E., Di Pilato, P., Herth, M. M., Lehel, S., Ettrup, A., Lykke Andersen, V., Dyssegaard, A., De Giorgio, P., Perrone, R., Berardi, F., Colabufo, N. A., Niso, M., Knudsen, G. M., & Leopoldo, M. (2014). Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor. European Journal of Medicinal Chemistry, 79, 152-63. https://doi.org/10.1016/j.ejmech.2014.03.066

Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor. / Hansen, Hanne D; Lacivita, Enza; Di Pilato, Pantaleo et al.
I: European Journal of Medicinal Chemistry, Bind 79, 22.05.2014, s. 152-63.

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

Hansen, HD, Lacivita, E, Di Pilato, P, Herth, MM, Lehel, S, Ettrup, A, Lykke Andersen, V, Dyssegaard, A, De Giorgio, P, Perrone, R, Berardi, F, Colabufo, NA, Niso, M, Knudsen, GM & Leopoldo, M 2014, 'Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor', European Journal of Medicinal Chemistry, bind 79, s. 152-63. https://doi.org/10.1016/j.ejmech.2014.03.066

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title = "Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor",

abstract = "In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [(11)C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7 receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [(11)C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7 receptor PET radioligands.",

author = "Hansen, {Hanne D} and Enza Lacivita and {Di Pilato}, Pantaleo and Herth, {Matthias M} and Szabolcs Lehel and Anders Ettrup and {Lykke Andersen}, Valdemar and Agnete Dyssegaard and {De Giorgio}, Paola and Roberto Perrone and Francesco Berardi and Colabufo, {Nicola Antonio} and Mauro Niso and Knudsen, {Gitte M} and Marcello Leopoldo",

year = "2014",

month = may,

day = "22",

doi = "10.1016/j.ejmech.2014.03.066",

language = "English",

volume = "79",

pages = "152--63",

journal = "European Journal of Medicinal Chemistry",

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publisher = "Elsevier France Editions Scientifiques et Medicales",

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TY - JOUR

T1 - Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor

AU - Hansen, Hanne D

AU - Lacivita, Enza

AU - Di Pilato, Pantaleo

AU - Herth, Matthias M

AU - Lehel, Szabolcs

AU - Ettrup, Anders

AU - Lykke Andersen, Valdemar

AU - Dyssegaard, Agnete

AU - De Giorgio, Paola

AU - Perrone, Roberto

AU - Berardi, Francesco

AU - Colabufo, Nicola Antonio

AU - Niso, Mauro

AU - Knudsen, Gitte M

AU - Leopoldo, Marcello

PY - 2014/5/22

Y1 - 2014/5/22

N2 - In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [(11)C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7 receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [(11)C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7 receptor PET radioligands.

AB - In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [(11)C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7 receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [(11)C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7 receptor PET radioligands.

U2 - 10.1016/j.ejmech.2014.03.066

DO - 10.1016/j.ejmech.2014.03.066

M3 - Journal article

C2 - 24732791

SN - 0223-5234

VL - 79

SP - 152

EP - 163

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Synthesis, radiolabeling and in vivo evaluation of [(11)C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT(7) receptor

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