Recently, a novel series of 2-phenylpyrazolo[1,5-a]pyrimidineacetamides has been reported as selective ligands of the translocator protein (18 kDa). Within this series, DPA-714 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide, Ki=7.0 nM) is a compound, which had been designed with a fluorine atom in its structure, allowing labelling with fluorine-18 (half-life: 109.8 min) and in vivo imaging using positron emission tomography. DPA-714 and its tosyloxy derivative (N,N-diethyl-2-(2-(4-(2-toluenesulfonyloxyethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) as precursor for the labelling with fluorine-18 were synthesized in two steps from DPA-713 (N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) and obtained in 32 and 42% yields, respectively. [18F]DPA-714 was synthesized using a simple one-step process (a tosyloxy-for-fluorine nucleophilic aliphatic substitution), which has been fully automated on our Zymate-XP robotic system. It involves: (A) reaction of K[18F]F-Kryptofix®222 with the tosyloxy precursor (4.5–5.0 mg, 8.2–9.1 µmol) at 165°C for 5 min in dimethyl sufloxide (0.6 mL) followed by (B) C18 PrepSep cartridge pre-purification and finally (C) semi-preparative high-performance liquid chromatography (HPLC) purification on a Waters X-Terra™ RP18. Typically, 5.6–7.4 GBq of [18F]DPA-714 (>95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111 GBq/µmol within 85–90 min (HPLC purification and SepPak®-based formulation included), starting from a 37 GBq [18F]fluoride batch (overall non-decay-corrected and isolated radiochemical yield: 15–20%). Copyright © 2008 John Wiley & Sons, Ltd.
最近,有报道称一种新型 2-苯基
吡唑并[1,5-a]
嘧啶乙酰胺系列可作为转运体蛋白(18 kDa)的选择性
配体。在这个系列中,DPA-714(N,N-二乙基-2-(2-(4-(2-
氟乙氧基)苯基)-5,7-二甲基
吡唑并[1,5-a]
嘧啶-3-基)乙酰胺,Ki=7.0 nM)是一种化合物,其结构中含有一个
氟原子,可以用
氟-18标记(半衰期:109.8 分钟),并使用正电子发射断层扫描进行体内成像。DPA-714 及其对
甲苯磺酰氧基衍
生物(N,N-二乙基-2-(2-(4-(2-
甲苯磺酰氧基乙氧基)苯基)-5,7-二甲基
吡唑并[1,5-a]
嘧啶-3-基)乙酰胺)作为用
氟-18 标记的前体,是由 DPA-713 (N、N-
二乙基-2-(2-(4-
甲氧基苯基)-5,7-二甲基
吡唑并[1,5-a]
嘧啶-3-基)乙酰胺)为前体,分两步合成了[18F]DPA-714,收率分别为 32% 和 42%。[18F]DPA-714采用简单的一步法合成(对
甲苯磺酰氧基对
氟的亲核脂肪族取代),在我们的Zymate-XP机器人系统上实现了全自动化。它包括:(A) K[18F]F-Kryptofix®222 与对
甲苯磺酰氧基前体(4.5-5.0 毫克,8.2-9.1 微摩尔)在 165°C 下于
二甲基亚砜(0.6 毫升)中反应 5 分钟,然后 (B) C18 PrepSep 滤芯预纯化,最后 (C) 在 Waters X-Terra™ RP18 上进行半制备高效
液相色谱 (HPLC) 纯化。通常情况下,从一批 37 GBq [18F]
氟化物开始,在 85-90 分钟内可获得 5.6-7.4 GBq [18F]DPA-714 (
化学和放射
化学纯度大于 95%),比放射性活度范围为 37-111 GBq/µmol(包括 HPLC 纯化和基于 SepPak® 的配方)(总体非衰变校正和分离放射
化学收率:15-20%)。Copyright © 2008 John Wiley & Sons, Ltd. All Rights Reserved.