合成和评价[(1)(8)F] fluororasagiline,小说正电子发射断层扫描(PET)放射性配体为单胺氧化酶B(缺氧)。

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唠叨,莱曼L, Kettschau G,海因里希·T,蒂埃尔,Varrone, Gulyas B, Halldin C

合成和评价[(1)(8)F] fluororasagiline,小说正电子发射断层扫描(PET)放射性配体为单胺氧化酶B(缺氧)。

Bioorg医疗化学。2012年5月1日,20 (9):3065 - 71。doi: 10.1016 / j.bmc.2012.02.056。Epub 2012年3月3。

PubMed ID

22436387 (在PubMed

]

文摘

本研究的目的是合成和评价一种新型氟18标记的模拟rasagiline(6)作为单胺氧化酶B的宠物放射性配体(缺氧)。相应的非放射性fluorine-19配体(1 s, 2 s) 2-fluoro-n——(prop-2-yn-1-yl) indan-1-amine(4),在体外实验中为特征。前体化合物(3 8 ar) 3 - (prop-2-yn-1-yl) 3、3、8、8 a-tetrahydroindeno [1, 2 - d] [1, 2, 3] oxathiazole 2, 2-dioxide(3)和参考标准4在多步合成合成。重组体人缺氧和是酶制剂被用于IC(50)值以确定化合物4利用一个酶的测定采用kynuramine作为衬底。放射性标记是通过一个两步合成,影响亲核取代水解sulphamidate集团紧随其后。人类整个半球放射自显影法(ARG)与执行(18)F fluororasagiline。阻断试验吡吲哚(是),L-deprenyl和rasagiline(缺氧)的特异性进行了绑定。正电子发射断层扫描(PET)的一项研究是在一个时间活性曲线的猕猴猴全脑与高、低和地区缺氧活动记录。Radiometabolites测量在猴子等离子使用梯度高效液相色谱法。化合物4抑制缺氧的IC(50) 27海里,是IC(50)为2.3妈妈。 Radiolabeling of precursor 3 and subsequent hydrolysis of the protecting group towards (1S,2S)-2-[(18)F]fluoro-N-(prop-2-yn-1-yl)indan-1-amine (6) was successfully accomplished with an radiochemical yield of 40-70%, a radiochemical purity higher than 99% and a specific radioactivity higher than 200GBq/mumol. ARG demonstrated selective binding for [(18)F]fluororasagiline (6) to MAO-B containing brain regions, for example, striatum. The initial uptake in the monkey brain was 250% SUV at 4 min post injection. The highest amounts of radioactivity were observed in the striatum and thalamus as expected whereas in the cortex and cerebellum lower levels were observed. Metabolite studies demonstrated 30% unchanged radioligand at 90 min post injection. Our investigations demonstrated that the new ligand [(18)F]fluororasagiline (6) binds specifically to MAO-B in vitro and has a MAO-B specific binding pattern in vivo. Thus, it could serve as a novel potential candidate for human PET studies.

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绑定属性

药物	目标	财产	测量	pH值	温度(°C)
Rasagiline	胺氧化酶(flavin-containing) B	集成电路50 (nM)	46	N /一个	N /一个	细节
司立吉林	胺氧化酶(flavin-containing) B	集成电路50 (nM)	13	N /一个	N /一个	细节