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• W3087589871 abstract "Metabotropic glutamate receptor 2 (mGlu2) is a known target for treating several central nervous system (CNS) disorders. To develop a viable positron emission tomography (PET) ligand for mGlu2, we identified new candidates 5a-i that are potent negative allosteric modulators (NAMs) of mGlu2. Among these candidates, 4-(2-fluoro-4-methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide (5i, also named as [11C]MG2-1812) exhibited high potency, high subtype selectivity, and favorable lipophilicity. Compound 5i was labeled with positron-emitting carbon-11 (11C) to obtain [11C]5i in high radiochemical yield and high molar activity by O-[11C]methylation of the phenol precursor 12 with [11C]CH3I. In vitro autoradiography with [11C]5i showed heterogeneous radioactive accumulation in the brain tissue sections, ranked in the order: cortex > striatum > hippocampus > cerebellum ≫ thalamus > pons. PET study of [11C]5i indicated in vivo specific binding of mGlu2 in the rat brain. Based on the [11C]5i scaffold, further optimization for new candidates is underway to identify a more suitable ligand for imaging mGlu2." @default.
• W3087589871 created "2020-09-25" @default.
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• W3087589871 date "2020-09-22" @default.
• W3087589871 modified "2023-10-18" @default.
• W3087589871 title "Identification and Development of a New Positron Emission Tomography Ligand 4-(2-Fluoro-4-[11C]methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide for Imaging Metabotropic Glutamate Receptor Subtype 2 (mGlu2)" @default.
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• W3087589871 doi "https://doi.org/10.1021/acs.jmedchem.9b01991" @default.
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