Design, Synthesis, and Evaluation of 18F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes.
Zhen ChenWakana MoriHualong FuMichael A SchafrothAkiko HatoriTuo ShaoGenwei ZhangRichard S VanYiding ZhangKuan HuMasayuki FujinagaLu WangVasily BelovDaisuke OgasawaraPilar GiffenigXiaoyun DengJian RongQingzhen YuXiaofei ZhangMikhail I PapisovYihan ShaoThomas L CollierJun-An MaBenjamin F CravattLee JosephsonMing-Rong ZhangSteven H LiangPublished in: Journal of medicinal chemistry (2019)
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 6 (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.
Keyphrases
- positron emission tomography
- pet imaging
- computed tomography
- pet ct
- small molecule
- living cells
- fluorescence imaging
- single molecule
- resting state
- oxidative stress
- endothelial cells
- functional connectivity
- binding protein
- emergency department
- nucleic acid
- fluorescent probe
- transcription factor
- subarachnoid hemorrhage
- photodynamic therapy