Epoxy compounds usually have stronger nucleophilic ability, because the alkyl group on the oxygen atom makes the bond angle smaller, which makes the lone pair of electrons react more dissimilarly with the electron-deficient system. Compound: (6-Fluoropyridin-3-yl)methanol, is researched, Molecular C6H6FNO, CAS is 39891-05-9, about 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).Safety of (6-Fluoropyridin-3-yl)methanol.
Metabotropic glutamate receptor 2 (mGlu2) is a known target for treating several central nervous system (CNS) disorders. To develop a viable positron emission tomog. (PET) ligand for mGlu2, we identified new candidates 5a-i that are potent neg. 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 radiochem. yield and high molar activity by O-[11C]methylation of the phenol precursor 12 with [11C]CH3I. In vitro autoradiog. 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.
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