...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Synthesis and Evaluation of No-Carrier-Added 8-Cyclopentyl-3-(3-[~(18)F]fluoropropyl)-1-propylxanthine ([~(18)F]CPFPX): A Potent and Selective A_1-Adenosine Receptor Antagonist for in Vivo Imaging
【24h】

Synthesis and Evaluation of No-Carrier-Added 8-Cyclopentyl-3-(3-[~(18)F]fluoropropyl)-1-propylxanthine ([~(18)F]CPFPX): A Potent and Selective A_1-Adenosine Receptor Antagonist for in Vivo Imaging

机译：无载体添加的8-环戊基-3-（3- [〜（18）F]氟丙基）-1-丙基黄嘌呤（[〜（18）F] CPFPX）的合成和评价：一种有效的选择性A_1-腺苷受体。体内成像拮抗剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

This report describes the precursor synthesis and the no-carrier-added (nca) radiosynthesis of the new A_1 adenosine receptor (A_1AR) antagonist [~(18)F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylzanthine (CPFPX), 3~*, with fluorine-18 (half-life = 109.6 min). Nucleophilic radio-fluorination of the precursor tosylate 8-cyclopentyl-3-(3-tosyloxypropyl)-7-pivaloyloxymethyl-1-propylxanthine, 2, with nca [~(18)F]KF under aminopolyether-mediated conditions (Kryptofix 2.2.2/K_2CO_3) followed by deprotection was straightforward and, after formulation, gave the radioligand ready for injection with a radiochemical yield of 45 ± 7%, a radiochemical purity of >98% and a specific radioactivity of >270 GBq/μmol (>7.2 Ci/μmol). Preparation time averaged 55 min. The synthesis proved reliable for high batch yields (～7.5 GBq) in routine production (n = 120 runs). The radiotracer was pharmacologically evaluated in vitro and in vivo and its pharmacokinetics in rodents determined in detail. After iv injection a high accumulation of radioactivity occurred in several regions of mouse brain including thalamus, striatum, cortex, and cerebellum. Antagonism by the specific A_1AR antagonists 8-cyclopentyl-A_2AR antagonist 3,7-dimethyl-1-propargylzanthine (DMPX), indicated specific and reversible binding of the radioligand to A_1AR in cortical and subcortical regions of interest. In mouse blood at least two polar metabolites formed rapidly (50% at 5 min after tracer application). However, chromatographic analyses of brain homogenate extracts taken 60 min pi showed that >98% of radioactivity was unchanged radioligand. Chromatographic isolation and reinjection of peripherally formed radioactive metabolites revealed no accumulation of radioactivity in mouse brain, probably due to the polarity of the metabolites. These preliminary results suggest that nca [~(18)F]CPFPX is a useful radioligand for the noninvasive imaging of the brain A_1AR.
机译：这份报告描述了新的A_1腺苷受体（A_1AR）拮抗剂[〜（18）F] 8-环戊基-3-（3-氟丙基）-1-丙基花氨酸（的前体合成和无载体（nca）放射性合成（ CPFPX），3〜*，氟18（半衰期= 109.6分钟）。在氨基聚醚介导的条件下，用nca [〜（18）F] KF对前体甲苯磺酸酯化8-环戊基-3-（3-甲苯磺酰氧基丙基）-7-新戊酰氧基甲基-1-丙基黄嘌呤进行亲核放射性氟化（Kryptofix 2.2.2 / K_2CO_3），然后进行脱保护非常简单，配制后即可制备放射性配体以进行放射，其放射化学产率为45±7％，放射化学纯度为> 98％，比放射性为> 270 GBq /μmol（> 7.2 Ci /μmol）。准备时间平均为55分钟。事实证明，该合成方法可在常规生产（n = 120运行）中实现高批量（约7.5 GBq）的批量生产。对放射性示踪剂进行了体外和体内药理学评价，并详细测定了其在啮齿动物中的药代动力学。静脉注射后，在小鼠脑的多个区域（包括丘脑，纹状体，皮质和小脑）中发生了高放射性累积。特定的A_1AR拮抗剂8-环戊基-A_2AR拮抗剂3,7-二甲基-1-丙炔基鸟氨酸（DMPX）的拮抗作用表明，放射性配体与目标皮层和皮层下区域的A_1AR具有特异性且可逆的结合。在小鼠血液中，至少有两种极性代谢物迅速形成（在应用示踪剂后5分钟内达到50％）。但是，在pi 60分钟后对脑匀浆提取物进行的色谱分析表明，> 98％的放射性是不变的放射性配体。色谱分离和重新注入周围形成的放射性代谢物表明，在小鼠脑中没有放射性积聚，这可能是由于代谢物的极性所致。这些初步结果表明，nca [〜（18）F] CPFPX是用于大脑A_1AR的无创成像的有用放射性配体。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号