Synthesis and Pharmacological Characterization of the Selective GluK1 Radioligand (S)-2-Amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)

Anna Alcaide; Laura Marconi; Ales Marek; Isabell Haym; Birgitte Nielsen; Stine Møllerud; Mikael Jensen; Paola Conti; Darryl S Pickering; Lennart Bunch

doi:10.1039/c6md00339g

Synthesis and Pharmacological Characterization of the Selective GluK1 Radioligand (S)-2-Amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)

Anna Alcaide, Laura Marconi, Ales Marek, Isabell Haym, Birgitte Nielsen, Stine Møllerud, Mikael Jensen, Paola Conti, Darryl S Pickering, Lennart Bunch

14 Citationer (Scopus)

Abstract

The kainic acid receptors belong to the class of ionotropic glutamate receptors and comprise five subunits named GluK1-5. Radioligands are essential tools for use in binding assays aimed at ligand-receptor structure-activity-relationship studies. Previous work has led to the synthesis of GluK1 radioligands [3H]-SYM2081, [3H]-UBP310 and [3H]-ATPA, however all strategies were work-intensive and thus not attractive. Herein, we report the synthesis of [3H]-NF608 and subsequent pharmacological evaluation at homomeric recombinant rat GluK1 receptors. Binding affinities of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands.

Originalsprog	Engelsk
Tidsskrift	MedChemComm
Vol/bind	7
Sider (fra-til)	2136-2144
Antal sider	9
ISSN	2040-2503
DOI	https://doi.org/10.1039/c6md00339g
Status	Udgivet - 2016

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10.1039/c6md00339g

c6md00339gForlagets udgivne version, 848 KBLicens: CC BY

Citationsformater

Alcaide, A., Marconi, L., Marek, A., Haym, I., Nielsen, B., Møllerud, S., Jensen, M., Conti, P., Pickering, D. S., & Bunch, L. (2016). Synthesis and Pharmacological Characterization of the Selective GluK1 Radioligand (S)-2-Amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608). MedChemComm, 7, 2136-2144. https://doi.org/10.1039/c6md00339g

Alcaide, A, Marconi, L, Marek, A, Haym, I, Nielsen, B , Møllerud, S, Jensen, M, Conti, P, Pickering, DS & Bunch, L 2016, 'Synthesis and Pharmacological Characterization of the Selective GluK1 Radioligand (S)-2-Amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)', MedChemComm, bind 7, s. 2136-2144. https://doi.org/10.1039/c6md00339g

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title = "Synthesis and Pharmacological Characterization of the Selective GluK1 Radioligand (S)-2-Amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)",

abstract = "The kainic acid receptors belong to the class of ionotropic glutamate receptors and comprise five subunits named GluK1-5. Radioligands are essential tools for use in binding assays aimed at ligand-receptor structure-activity-relationship studies. Previous work has led to the synthesis of GluK1 radioligands [3H]-SYM2081, [3H]-UBP310 and [3H]-ATPA, however all strategies were work-intensive and thus not attractive. Herein, we report the synthesis of [3H]-NF608 and subsequent pharmacological evaluation at homomeric recombinant rat GluK1 receptors. Binding affinities of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands.",

author = "Anna Alcaide and Laura Marconi and Ales Marek and Isabell Haym and Birgitte Nielsen and Stine M{\o}llerud and Mikael Jensen and Paola Conti and Pickering, {Darryl S} and Lennart Bunch",

year = "2016",

doi = "10.1039/c6md00339g",

language = "English",

volume = "7",

pages = "2136--2144",

journal = "MedChemComm",

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publisher = "Royal Society of Chemistry",

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T1 - Synthesis and Pharmacological Characterization of the Selective GluK1 Radioligand (S)-2-Amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)

AU - Alcaide, Anna

AU - Marconi, Laura

AU - Marek, Ales

AU - Haym, Isabell

AU - Nielsen, Birgitte

AU - Møllerud, Stine

AU - Jensen, Mikael

AU - Conti, Paola

AU - Pickering, Darryl S

AU - Bunch, Lennart

PY - 2016

Y1 - 2016

N2 - The kainic acid receptors belong to the class of ionotropic glutamate receptors and comprise five subunits named GluK1-5. Radioligands are essential tools for use in binding assays aimed at ligand-receptor structure-activity-relationship studies. Previous work has led to the synthesis of GluK1 radioligands [3H]-SYM2081, [3H]-UBP310 and [3H]-ATPA, however all strategies were work-intensive and thus not attractive. Herein, we report the synthesis of [3H]-NF608 and subsequent pharmacological evaluation at homomeric recombinant rat GluK1 receptors. Binding affinities of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands.

AB - The kainic acid receptors belong to the class of ionotropic glutamate receptors and comprise five subunits named GluK1-5. Radioligands are essential tools for use in binding assays aimed at ligand-receptor structure-activity-relationship studies. Previous work has led to the synthesis of GluK1 radioligands [3H]-SYM2081, [3H]-UBP310 and [3H]-ATPA, however all strategies were work-intensive and thus not attractive. Herein, we report the synthesis of [3H]-NF608 and subsequent pharmacological evaluation at homomeric recombinant rat GluK1 receptors. Binding affinities of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands.

U2 - 10.1039/c6md00339g

DO - 10.1039/c6md00339g

M3 - Journal article

SN - 2040-2503

VL - 7

SP - 2136

EP - 2144

JO - MedChemComm

JF - MedChemComm

ER -

Synthesis and Pharmacological Characterization of the Selective GluK1 Radioligand (S)-2-Amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)

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