Synthesis and biological evaluation of (E)-3-styrylpyridine derivatives as amyloid imaging agents for Alzheimer's disease
Synthesis and biological evaluation of (E)-3-styrylpyridine derivatives as amyloid imaging agents for Alzheimer's disease
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DOI：
10.1016/j.nucmedbio.2005.01.006
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Kung, HF
中科院分区：
文献类型：
--
作者：
Ono, M;Haratake, M;Kung, HF
合成了一系列新的（E）-3-苯乙烯基吡啶衍生物，并对其作为阿尔茨海默病（AD）中淀粉样斑块的潜在诊断显像剂进行了研究。当使用AD脑匀浆进行体外结合研究时，使用一系列苯乙烯基吡啶衍生物，具有二甲氨基的（E）-2-溴-5-（4-二甲基氨基苯乙烯基）吡啶（7）显示出最高的结合亲和力。化合物7强烈染色神经炎和弥漫性斑块和脑血管淀粉样蛋白对死后AD脑切片。（E）-2-碘-5-（4-二甲基氨基苯乙烯基）吡啶（9），化合物7的碘代衍生物，也染色人AD切片中的老年斑。以三丁基锡衍生物为原料，以过氧化氢为氧化剂，通过碘代脱锡反应，成功地合成了放射性碘标记的配体[I-125]9。正常小鼠静脉注射[I-125]9后的生物分布研究显示，脑摄取高，洗脱快。综上所述，数据表明，新的放射性示踪剂，[I-125]9可能是有用的放射性碘标记的成像剂映射A β斑块在AD患者的大脑。(c)2005年爱思唯尔公司All rights reserved.
A new series of (E)-3-styrylpyridine derivatives as potential diagnostic imaging agents targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and examined. When in vitro binding studies using AD brain homogenates were carried out with a series of styrylpyridine derivatives, (E)-2-Bromo-5-(4-diinethylaminostyryl)pyridine (7) with a dimethylamino group showed the highest binding affinity. Compound 7 intensely stained neuritic and diffused plaques and cerebrovascular amyloids on postmortem AD brain sections. (E)-2-lodo-5-(4-dimethylaminostyryl)pyridine (9), the iodo derivative of compound 7, also stained senile plaques in human AD sections. The radioiodinated ligand [I-125]9 Was successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives using hydrogen peroxide as the oxidant in high yields and with high radiochemical purity. A biodistribution study in normal mice after an intravenous injection of [I-125]9 displayed high brain uptake and fast washout. Taken together, the data suggest that the new radio tracer, [I-125]9 may be useful as a radioiodinated imaging agent for mapping A beta plaques in the brains of patients with AD. (c) 2005 Elsevier Inc. All rights reserved.