Towards the preparation of radiolabeled 1-aryl-3-benzyl ureas: Radiosynthesis of [11C-carbonyl] AR-A014418 by [11C]CO2 fixation
Towards the preparation of radiolabeled 1-aryl-3-benzyl ureas: Radiosynthesis of [11C-carbonyl] AR-A014418 by [11C]CO2 fixation
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DOI：
10.1016/j.bmcl.2011.12.139
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发表时间：
2012-03-01
影响因子：
2.7
通讯作者：
Vasdev, Neil
中科院分区：
文献类型：
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作者：
Hicks, Justin W.;Wilson, Alan A.;Vasdev, Neil
高选择性糖原合酶激酶 3 (GSK-3) 抑制剂 N-(4-甲氧基苄基)-N'-(5-硝基-1,3-噻唑-2-基) 尿素 (AR-A014418) 通过 [C-11]CO2 固定在尿素部分用碳 11（C-11；半衰期 = 20.4 分钟）进行放射性标记。 [C-11]CO2与4-甲氧基苄胺在CO2固定碱存在下反应，然后用POCl3脱水并添加2-氨基-5-硝基噻唑，制备[C-11-羰基]AR-A014418。基于 [C-11]CO2，该反应产生 8% 的未校正放射化学产率，并在 30 分钟内具有高比活性 (4 Ci/mu mol)。体外 GSK-3 β 酶活性测定表明 AR-A014418 (K-i = 770 nM) 并不像之前声称的那样有效。本文描述的[C-11]CO 2 固定方法应证明普遍适用于制备1-芳基-3-苄基-[C-11-羰基]脲作为正电子发射断层扫描的放射性示踪剂。 (C) 2012 Elsevier Ltd. 保留所有权利。
The highly selective glycogen synthase kinase-3 (GSK-3) inhibitor N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl) urea (AR-A014418) was radiolabeled with carbon-11 (C-11; half-life = 20.4 min) at the urea moiety via [C-11]CO2 fixation. Reaction of [C-11]CO2 with 4-methoxybenzylamine in the presence of a CO2 fixating base was followed by dehydration with POCl3 and addition of 2-amino-5-nitrothiazole to prepare [C-11-carbonyl] AR-A014418. This reaction resulted in an 8% uncorrected radiochemical yield, based on [C-11]CO2, with high specific activity (4 Ci/mu mol) within 30 min. An in vitro GSK-3 beta enzyme activity assay revealed that AR-A014418 (K-i = 770 nM) is not as potent as previously claimed. The [C-11]CO2 fixation methodology described herein should prove generally applicable to preparing 1-aryl-3-benzyl-[C-11-carbonyl] ureas as radiotracers for positron emission tomography. (C) 2012 Elsevier Ltd. All rights reserved.