Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor
Research output: Contribution to journal › Journal article › Research › peer-review
In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [(11)C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7 receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [(11)C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7 receptor PET radioligands.
Original language | English |
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Journal | European Journal of Medicinal Chemistry |
Volume | 79 |
Pages (from-to) | 152-163 |
Number of pages | 12 |
ISSN | 0223-5234 |
DOIs | |
Publication status | Published - 2014 |
- Animals, Brain, CHO Cells, Carbon Isotopes, Cricetulus, HEK293 Cells, Humans, Kinetics, Ligands, Molecular Structure, Phenols, Piperazines, Positron-Emission Tomography, Propanols, Pyrazines, Radiopharmaceuticals, Receptors, Serotonin, Sulfonamides, Swine, Tissue Distribution
Research areas
ID: 138502303