1252676-41-7Relevant academic research and scientific papers
Design, synthesis, radiolabeling, and in vivo evaluation of carbon-11 labeled N -[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a potential positron emission tomography tracer for the dopamine D4 receptors
Lacivita, Enza,De Giorgio, Paola,Lee, Irene T.,Rodeheaver, Sean I.,Weiss, Bryan A.,Fracasso, Claudia,Caccia, Silvio,Berardi, Francesco,Perrone, Roberto,Zhang, Ming-Rong,Maeda, Jun,Higuchi, Makoto,Suhara, Tetsuya,Schetz, John A.,Leopoldo, Marcello
, p. 7344 - 7355 (2010)
Here we describe the design, synthesis, and evaluation of physicochemical and pharmacological properties of D4 dopamine receptor ligands related to N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (2). Structural features were incorporated to increase affinity for the target receptor, to improve selectivity over D2 and σ1 receptors, to enable labeling with carbon-11 or fluorine-18, and to adjust lipophilicity within the range considered optimal for brain penetration and low nonspecific binding. Compounds 7 and 13 showed the overall best characteristics: nanomolar affinity for the D4 receptor, >100-fold selectivity over D2 and D3 dopamine receptors, 5-HT1A, 5-HT2A, and 5-HT2C serotonin receptors and σ1 receptors, and log-P = 2.37-2.55. Following intraperitoneal administration in mice, both compounds rapidly entered the central nervous system. The methoxy of N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3- methoxybenzamide (7) was radiolabeled with carbon-11 and subjected to PET analysis in non-human primate. [11C]7 time-dependently accumulated to saturation in the posterior eye in the region of the retina, a tissue containing a high density of D4 receptors.
In vitro and in vivo evaluation of N-{2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3-[11C]methoxybenzamide, a positron emission tomography (PET) radioligand for dopamine D4 receptors, in rodents
Leopoldo, Marcello,Selivanova, Svetlana V.,Müller, Adrienne,Lacivita, Enza,Schetz, John A.,Ametamey, Simon M.
, p. 1298 - 1308 (2014)
The D4 dopamine receptor belongs to the D2-like family of dopamine receptors, and its exact regional distribution in the central nervous system is still a matter of considerable debate. The availability of a selective radioligand for the D4 receptor with suitable properties for positron emission tomography (PET) would help resolve issues of D4 receptor localization in the brain, and the presumed diurnal change of expressed protein in the eye and pineal gland. We report here on in vitro and in vivo characteristics of the high-affinity D4 receptor-selective ligand N-{2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3-[11C]methoxybenzamide ([11C]2) in rat. The results provide new insights on the in vitro properties that a brain PET dopamine D4 radioligand should possess in order to have improved in vivo utility in rodents.
