Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N-methyl-D-aspartate receptor

Publication type:
Journal article
Metadata:
Autoren
  • A Bauman
  • M Piel
  • S Hoehnemann
  • A Krauss
  • M Jansen
  • C Solbach
  • G Dannhardt
  • F Roesch
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000295901500011&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1002/jlcr.1901
Externe Identifier
  • Clarivate Analytics Document Solution ID: 833RB
ISSN
0362-4803
Ausgabe der Veröffentlichung
9-10
Zeitschrift
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
Schlüsselwörter
  • glutamate
  • NMDA receptor
  • glycine binding site
  • (18)F-fluoroalkylation
  • (11)C-methylation
Paginierung
645 - 656
Datum der Veröffentlichung
2011
Status
Published
Titel
Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the <i>N</i>-methyl-D-aspartate receptor
Sub types
  • Article
Ausgabe der Zeitschrift
54

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>The <jats:italic>N</jats:italic>‐methyl‐ <jats:sc>d</jats:sc>‐aspartate (NMDA) receptor as a type of ionotropic glutamatergic receptors is essential for physiological processes such as learning, memory and synaptic plasticity. A glutamate‐induced overactivation of these receptors, accompanied by increased intracellular calcium concentration, causes cell injury and leads to a large number of acute or chronic neurological disorders, such as stroke, trauma, Parkinson's disease and Alzheimer's disease. In an attempt to visualise the glutamatergic neurotransmission <jats:italic>in vivo</jats:italic> with positron emission tomography, novel fluoroethoxy‐ and methoxy‐substituted reference compounds based on the lead structure of a hydantoin‐substituted indole‐2‐carboxylic acid were synthesised. The affinities towards the glycine binding site of the NMDA receptor showed <jats:italic>K</jats:italic><jats:sub>i</jats:sub> values between 322 and 11 nM and the lipophilicities ranged from log<jats:italic>D</jats:italic> values of 1.51 to 2.53. On the basis of these results, precursor compounds were synthesised containing a phenolic hydroxy moiety to obtain the radiolabelled ligands through an alkylation reaction. Radiosynthesis was achieved by labelling the precursor ethyl 4,6‐dichloro‐3‐((3‐(4‐hydroxyphenyl)‐2,4‐dioxoimidazolidin‐1‐yl)methyl)‐indole‐2‐carboxylate with 2‐[<jats:sup>18</jats:sup>F]fluoroethyl tosylate or [<jats:sup>11</jats:sup>C]methyl iodide and subsequent cleavage of the ethyl ester moiety. This gave the final products in overall decay‐corrected radiochemical yields of 5–7% and 6–9% and specific activities of 24–67 GBq/µmol and 8–26 GBq/µmol, respectively.</jats:p>
Autoren
  • A Bauman
  • M Piel
  • S Höhnemann
  • A Krauss
  • M Jansen
  • C Solbach
  • G Dannhardt
  • F Rösch
DOI
10.1002/jlcr.1901
eISSN
1099-1344
ISSN
0362-4803
Ausgabe der Veröffentlichung
10
Zeitschrift
Journal of Labelled Compounds and Radiopharmaceuticals
Sprache
en
Online publication date
2011
Paginierung
645 - 656
Datum der Veröffentlichung
2011
Status
Published
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1002/jlcr.1901
Datum der Datenerfassung
2023
Titel
Synthesis, labelling and evaluation of hydantoin‐substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the <i>N</i>‐methyl‐<scp>d</scp>‐aspartate receptor
Ausgabe der Zeitschrift
54

Data source: Crossref

Autoren
  • A Bauman
  • M Piel
  • S Höhnemann
  • A Krauss
  • M Jansen
  • C Solbach
  • G Dannhardt
  • F Rösch
Zeitschrift
Journal of Labelled Compounds and Radiopharmaceuticals
Artikelnummer
10
Paginierung
645 - 656
Datum der Veröffentlichung
2011
Herausgeber
John Wiley & Sons, Ltd Chichester, UK
Datum der Datenerfassung
2021
Titel
Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N-methyl-D-aspartate receptor
Sub types
  • article
Ausgabe der Zeitschrift
54

Data source: Manual

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