Synthesis and evaluation of novel N-fluoropyridyl derivatives of tropane as potential PET imaging agents for the dopamine transporter.
Synthesis and evaluation of novel N-fluoropyridyl derivatives of tropane as potential PET imaging agents for the dopamine transporter.
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DOI：
10.1016/j.bmcl.2011.03.051
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发表时间：
2011-05-15
影响因子：
2.7
通讯作者：
Kung HF
中科院分区：
文献类型：
--
作者：
Liu J;Zhu L;Plössl K;Lieberman BP;Kung HF
合成了一系列新的含N-氟吡啶的托烷类化合物，并通过竞争性放射配基结合分析测定了它们与多巴胺转运体(DAT)、5-羟色胺转运体(SERT)和去甲肾上腺素(NET)的结合亲和力。其中，化合物6d与DAT的结合亲和力最高(Ki=4.1 nM)，对DAT的选择性高于SERT(5倍)和Net(16倍)。化合物6d分两步用氟-18放射性标记。[18F]6d的区域脑分布和体外放射自显影研究表明，该配体选择性地定位在纹状体区域，在那里DAT结合位点高度表达。[18F]6D可能作为一种潜在的放射性配基用于PET成像DAT。
A series of novel N-fluoropyridyl-containing tropane derivatives were synthesized and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine (NET) were determined via competitive radioligand binding assays. Among these derivatives, compound 6d showed the highest binding affinity to DAT (Ki = 4.1 nM), and selectivity for DAT over SERT (5 fold) and NET (16 fold). Compound 6d was radiolabeled with Fluorine-18 in two steps. Regional brain distribution and ex vivo autoradiography studies of [18F]6d demonstrated that the ligand was selectively localized in the striatum region, where DAT binding sites are highly expressed. [18F]6d may be useful as a potential radioligand for imaging DATs with PET.