Synthesis and biological evaluation of novel carbon-11 labeled pyridyl ethers: candidate ligands for in vivo imaging of alpha4beta2 nicotinic acetylcholine receptors (alpha4beta2-nAChRs) in the brain with positron emission tomography.
Synthesis and biological evaluation of novel carbon-11 labeled pyridyl ethers: candidate ligands for in vivo imaging of alpha4beta2 nicotinic acetylcholine receptors (alpha4beta2-nAChRs) in the brain with positron emission tomography.
复制标题
新型碳11标记吡啶醚的合成和生物学评价：用于大脑中α4β2烟碱乙酰胆碱受体（α4β2-nAChRs）正电子发射断层扫描体内成像的候选配体。
DOI：
10.1016/j.bmc.2009.05.021
复制
发表时间：
2009
影响因子：
3.5
通讯作者：
Horti,AndrewG
中科院分区：
文献类型：
--
作者：
Gao,Yongjun;Ravert,HaydenT;Kuwabara,Hiroto;Xiao,Yingxian;Endres,ChristopherJ;Hilton,John;Holt,DanielP;Kumar,Anil;Alexander,Mohab;Wong,DeanF;Dannals,RobertF;Horti,AndrewG
α4β2是脑烟碱型乙酰胆碱受体（nAChR）中最丰富的亚型，在多种脑功能和病理状态中起着关键作用。适用于通过正电子发射断层扫描（PET）可视化和定量α4β2 nAChR的成像剂将为确定nAChR在活体人脑中的功能和药理学提供独特的机会。在这项研究中，我们报告的合成，nAChR结合亲和力，和药理学性质的几个新的3-吡啶基醚化合物。大多数衍生物对nAChR具有高亲和力，对α4β2-nAChR具有高亚型选择性。这些新型nAChR配体中的三种用正电子发射同位素11 C进行放射性标记，并在动物研究中作为潜在的PET放射性示踪剂进行评估，用于脑nAChR成像并改善脑动力学。
The most abundant subtype of cerebral nicotinic acetylcholine receptors (nAChR), α4β2, plays a critical role in various brain functions and pathological states. Imaging agents suitable for visualization and quantification of α4β2 nAChRs by positron emission tomography (PET) would present unique opportunities to define the function and pharmacology of the nAChRs in the living human brain. In this study, we report the synthesis, nAChR binding affinity, and pharmacological properties of several novel 3-pyridyl ether compounds. Most of these derivatives displayed a high affinity to the nAChR and a high subtype selectivity for α4β2-nAChR. Three of these novel nAChR ligands were radiolabeled with the positron-emitting isotope11C and evaluated in animal studies as potential PET radiotracers for imaging of cerebral nAChRs with improved brain kinetics.