@article{oai:repo.qst.go.jp:00047207,
 author = {Oi, Norihito and Suzuki, Michiyuki and Terauchi, Taro and Tokunaga, Masaki and Nakatani, Yosuke and Yamamoto, Noboru and Fukumura, Toshimitsu and Zhang, Ming-Rong and Suhara, Tetsuya and Higuchi, Makoto and 大井 紀人 and 鈴木 成教 and 徳永 正希 and 中谷 陽介 and 張 明栄 and 須原 哲也 and 樋口 真人},
 issue = {16},
 journal = {Journal of medicinal chemistry},
 month = {Aug},
 note = {Orexin receptors (OXRs) in the brain have been implicated in diverse physiological and neuropsychiatric conditions. Here we describe the design, synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4-methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission tomography (PET) imaging. Structural features were incorporated to increase binding affinity for OXRs, to enable carbon-11 radiolabeling, and to adjust lipophilicity considered optimal for brain penetration and low nonspecific binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat brain sections showed that specific binding of [(11)C]9a was distributed primarily to neocortical layer VI and hypothalamus, consistent with reported localizations of orexin-2 receptors (OX2Rs). In vivo PET study of [(11)C]9a demonstrated moderate uptake of radioactivity into rat and monkey brains under deficiency or blockade of P-glycoprotein, and distribution of PET signals in the brain was in agreement with autoradiographic data. Our approach and findings have provided significant information for development of OX2R PET tracers.},
 pages = {6371--6385},
 title = {Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor.},
 volume = {56},
 year = {2013}
}