@article{oai:repo.qst.go.jp:00047213,
 author = {Lacivita, Enza and De, Giorgio Paola and T, Lee Irene and I, Rodeheaver Sean and A, Weiss Bryan and Fracasso, Claudia and Caccia, Silvio and Berardi, Francesco and Perrone, Roberto and Zhang, Ming-Rong and Maeda, Jun and Higuchi, Makoto and Suhara, Tetsuya and A, Schetz John and Leopoldo, Marcello and 張 明栄 and 前田 純 and 樋口 真人 and 須原 哲也},
 issue = {20},
 journal = {Journal of medicinal chemistry},
 month = {Oct},
 note = {Here we describe the design, synthesis, and evaluation of physicochemical and pharmacological properties of D(4) 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 D(2) and σ(1) 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 D(4) receptor, >100-fold selectivity over D(2) and D(3) dopamine receptors, 5-HT(1A), 5-HT(2A), and 5-HT(2C) serotonin receptors and σ(1) 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. [(11)C]7 time-dependently accumulated to saturation in the posterior eye in the region of the retina, a tissue containing a high density of D(4) receptors.},
 pages = {7344--7355},
 title = {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 D(4) receptors.},
 volume = {53},
 year = {2010}
}