Design, Synthesis, and Evaluation of ¹⁸F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes

Abstract

Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound <b>6</b> (identified from a therapeutic agent) was advanced for ¹⁸F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel ¹⁸F-labeled MAGL PET probes.