Synthesis and Initial Characterization of a Selective, Pseudo-irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer.

ABSTRACT: 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 ¹⁸ F 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 durat

SUBMITTER: Gentzsch C 

PROVIDER: S-EPMC8247983 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature