Impact of hydroxy moieties at the benzo[7]annulene ring system of GluN2B ligands: Design, synthesis and biological evaluation.

Cytoprotective activity Docking studies GluN2B selective antagonists Ifenprodil binding site Metabolic stability NMDA receptor Negative allosteric modulators Selectivity Structure-activity relationships Structure-affinity relationships

Journal

Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298

Informations de publication

Date de publication:
01 12 2019
Historique:
received: 29 07 2019
revised: 25 09 2019
accepted: 28 09 2019
pubmed: 28 10 2019
medline: 25 9 2020
entrez: 26 10 2019
Statut: ppublish

Résumé

In this study, the impact of one or two hydroxy moieties at the benzo[7]annulene scaffold on the GluN2B affinity and cytoprotective activity was analyzed. The key intermediate for the synthesis of OH-substituted benzo[7]annulenamines 11-13 and 17 was the epoxyketone 8. Reductive epoxide opening of 8 resulted with high regioselectivity in the 5-hydroxyketone 9 (Pd(OAc)

Identifiants

pubmed: 31648876
pii: S0968-0896(19)31300-8
doi: 10.1016/j.bmc.2019.115146
pii:
doi:

Substances chimiques

Bridged Bicyclo Compounds 0
Ligands 0
NR2B NMDA receptor 0
Receptors, N-Methyl-D-Aspartate 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

115146

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Louisa Temme (L)

Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), Westfälische Wilhelms-Universität Münster, Germany.

Frederik Börgel (F)

Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany.

Dirk Schepmann (D)

Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany.

Dina Robaa (D)

Institut für Pharmazie der Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany.

Wolfgang Sippl (W)

Institut für Pharmazie der Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany.

Constantin Daniliuc (C)

Organisch-chemisches Institut der Westfälischen Wilhelms-Universität, Münster, Corrensstraße 40, 48149 Münster, Germany.

Bernhard Wünsch (B)

Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), Westfälische Wilhelms-Universität Münster, Germany. Electronic address: wuensch@uni-muenster.de.

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Classifications MeSH