Synthesis and Initial Characterization of a Selective, Pseudo‐irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer
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- The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine‐based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo‐irreversible binding mode. We demonstrate a novel protecting groupThe enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine‐based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo‐irreversible binding mode. We demonstrate a novel protecting group strategy for 18F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution.…
Autor(en): | Christian Gentzsch, Matthias Hoffmann, Yasuhiro Ohshima, Naoko Nose, Xinyu Chen, Takahiro Higuchi, Michael Decker |
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URN: | urn:nbn:de:bvb:20-opus-239904 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin |
Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | ChemMedChem |
Erscheinungsjahr: | 2021 |
Band / Jahrgang: | 16 |
Heft / Ausgabe: | 9 |
Erste Seite: | 1427 |
Letzte Seite: | 1437 |
Originalveröffentlichung / Quelle: | ChemMedChem 2021, 16(9):1427-1437. DOI: 10.1002/cmdc.202000942 |
DOI: | https://doi.org/10.1002/cmdc.202000942 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Freie Schlagwort(e): | carbamate; enzyme kinetics; fluorine-18; positron emission tomography; radiotracers |
Datum der Freischaltung: | 23.12.2021 |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |