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 Citations (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.

Original language	English
Journal	MedChemComm
Volume	7
Pages (from-to)	2136-2144
Number of pages	9
ISSN	2040-2503
DOIs	https://doi.org/10.1039/c6md00339g
Publication status	Published - 2016

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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

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). / Alcaide, Anna; Marconi, Laura; Marek, Ales et al.

In: MedChemComm, Vol. 7, 2016, p. 2136-2144.

Research output: Contribution to journal › Journal article › Research › peer-review

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, vol. 7, pp. 2136-2144. https://doi.org/10.1039/c6md00339g

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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.",

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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

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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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