In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain.


Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 09 2021
Historique:
received: 07 05 2021
revised: 30 06 2021
accepted: 05 07 2021
pubmed: 14 7 2021
medline: 5 1 2022
entrez: 13 7 2021
Statut: ppublish

Résumé

Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder l-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (K

Identifiants

pubmed: 34256118
pii: S0960-894X(21)00481-9
doi: 10.1016/j.bmcl.2021.128254
pii:
doi:

Substances chimiques

Indans 0
Monoamine Oxidase Inhibitors 0
indacrinone B926Y9U4QN
Monoamine Oxidase EC 1.4.3.4

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

128254

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Sladjana Dukić-Stefanović (S)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany.

Thu Hang Lai (T)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany; ROTOP Pharmaka GmbH, Department of Research and Development, 01328 Dresden, Germany.

Magali Toussaint (M)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany.

Oliver Clauß (O)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany.

Ivana I Jevtić (II)

University of Belgrade-Institute of Chemistry, Technology and Metallurgy, Department of Chemistry, Njegoševa 12, 11000 Belgrade, Serbia.

Jelena Z Penjišević (JZ)

University of Belgrade-Institute of Chemistry, Technology and Metallurgy, Department of Chemistry, Njegoševa 12, 11000 Belgrade, Serbia.

Deana Andrić (D)

University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11158 Belgrade, Serbia.

Friedrich-Alexander Ludwig (FA)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany.

Daniel Gündel (D)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany.

Winnie Deuther-Conrad (W)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany.

Sladjana V Kostić-Rajačić (SV)

University of Belgrade-Institute of Chemistry, Technology and Metallurgy, Department of Chemistry, Njegoševa 12, 11000 Belgrade, Serbia.

Peter Brust (P)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany.

Rodrigo Teodoro (R)

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research site Leipzig, 04318 Leipzig, Germany. Electronic address: r.teodoro@hzdr.de.

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Classifications MeSH