TY  - JOUR
A1  - Gentzsch, Christian
A1  - Hoffmann, Matthias
A1  - Ohshima, Yasuhiro
A1  - Nose, Naoko
A1  - Chen, Xinyu
A1  - Higuchi, Takahiro
A1  - Decker, Michael
T1  - Synthesis and Initial Characterization of a Selective, Pseudo‐irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer
T2  - ChemMedChem
N2  - 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 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.
KW  - carbamate
KW  - enzyme kinetics
KW  - fluorine-18
KW  - positron emission tomography
KW  - radiotracers
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23990
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-239904
VL  - 16
IS  - 9
SP  - 1427
EP  - 1437
ER  -