Open AccessDesign, Synthesis, and Evaluation of 18F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes
Author(s) -
Zhen Chen,
Wakana Mori,
Hualong Fu,
Michael A. Schafroth,
Akiko Hatori,
Tuo Shao,
Genwei Zhang,
Richard Van,
Yiding Zhang,
Kuan Hu,
Masayuki Fujinaga,
Lu Wang,
Vasily Belov,
Daisuke Ogasawara,
Pilar Giffenig,
Xiaoyun Deng,
Jian Rong,
Qingzhen Yu,
Xiaofei Zhang,
Mikhail Papisov,
Yihan Shao,
Thomas Collier,
JunAn Ma,
Benjamin F. Cravatt,
Lee Josephson,
MingRong Zhang,
Steven H. Liang
Publication year - 2019
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.9b00936
Subject(s) - monoacylglycerol lipase , chemistry , positron emission tomography , ligand (biochemistry) , radiosynthesis , pet imaging , combinatorial chemistry , biochemistry , endocannabinoid system , nuclear medicine , medicine , receptor
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 18 F-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 18 F-labeled MAGL PET probes.