Abstract
The discovery of a structurally distinct cannabinoid-1 receptor (CB1R) positron emission tomography tracer is described. Starting from an acyclic amide CB1R inverse agonist (1) as the lead compound, an efficient route to introduce 18F to the molecule was developed. Further optimization focused on reducing the lipophilicity and increasing the CB1R affinity. These efforts led to the identification of [18F]-16 that exhibited good brain uptake and an excellent signal-to-noise ratio in rhesus monkeys.
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacokinetics
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Animals
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Brain / diagnostic imaging
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Brain / metabolism
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CHO Cells
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Cricetinae
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Cricetulus
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Fluorine Radioisotopes*
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Humans
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Macaca mulatta
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Positron-Emission Tomography
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacokinetics
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Radioligand Assay
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Radiopharmaceuticals / chemical synthesis*
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / pharmacokinetics
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Receptor, Cannabinoid, CB1 / metabolism*
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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Amides
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Fluorine Radioisotopes
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N-(2-(3-cyanophenyl)-3-(4-(2-fluoroethoxy)phenyl)-1-methylpropyl)-2-methyl-2-((5-methylpyridin-2-yl)oxy)propanamide
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Pyridines
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Radiopharmaceuticals
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Receptor, Cannabinoid, CB1
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Recombinant Proteins