1450591-86-2Relevant academic research and scientific papers
Synthesis and evaluation of 1-[2-(4-[11C]methoxyphenyl)phenyl] piperazine for imaging of the serotonin 5-HT7 receptor in the rat brain
Shimoda, Yoko,Yui, Joji,Xie, Lin,Fujinaga, Masayuki,Yamasaki, Tomoteru,Ogawa, Masanao,Nengaki, Nobuki,Kumata, Katsushi,Hatori, Akiko,Kawamura, Kazunori,Zhang, Ming-Rong
, p. 5316 - 5322 (2013)
1-[2-(4-Methoxyphenyl)phenyl]piperazine (4) is a potent serotonin 5-HT 7 receptor antagonist (Ki = 2.6 nM) with a low binding affinity for the 5-HT1A receptor (Ki = 476 nM). As a potential positron emission tomography (PET) radiotracer for the 5-HT 7 receptor, [11C]4 was synthesized at high radiochemical yield and specific activity, by O-[11C]methylation of 2′-(piperazin-1-yl)-[1,1′-biphenyl]-4-ol (6) with [ 11C]methyl iodide. Autoradiography revealed that [11C]4 showed in vitro specific binding with 5-HT7 in the rat brain regions, such as the thalamus which is a region with high 5-HT7 expression. Metabolite analysis indicated that intact [11C]4 in the brain exceeded 90% of the radioactive components at 15 min after the radiotracer injection, although two radiolabeled metabolites were found in the rat plasma. The PET study of rats showed moderated uptake of [11C]4 in the brain (1.2 SUV), but no significant regional difference in radioactivity in the brain. Pretreatment with 5-HT7-selective antagonist SB269970 (3) did not decrease the uptake of [11C]4 in the rat brain. Further studies are warranted that focus on the development of PET ligand candidates with higher binding affinity for 5-HT7 and higher in vivo stability in brain than 4.
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-HT7receptor
Hansen, Hanne D.,Lacivita, Enza,Di Pilato, Pantaleo,Herth, Matthias M.,Lehel, Szabolcs,Ettrup, Anders,Andersen, Valdemar L.,Dyssegaard, Agnete,De Giorgio, Paola,Perrone, Roberto,Berardi, Francesco,Colabufo, Nicola Antonio,Niso, Mauro,Knudsen, Gitte M.,Leopoldo, Marcello
, p. 152 - 163 (2014/05/06)
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, [11C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [11C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7receptor PET radioligands.
