Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson's disease

被引：18
作者：
Wang, Min [1 ]
Gao, Mingzhang [1 ]
Xu, Zhidong [2 ]
Zheng, Qi-Huang [1 ]
机构：
[1] Indiana Univ, Sch Med, Dept Radiol & Imaging Sci, 1345 West 16th St,Room 202, Indianapolis, IN 46202 USA
[2] Hebei Univ, Minist Educ, Coll Chem & Environm Sci, Key Lab Med Chem & Mol Diag, Baoding 071002, Hebei, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 06期
基金：
美国国家科学基金会;
关键词：
C-11]HG-10-102-01; Leucine-rich repeat kinase 2 (LRRK2); Radiosynthesis; Positron emission tomography (PET); Parkinson's disease (PD); FULLY AUTOMATED SYNTHESIS; HIGHLY POTENT; DISCOVERY; DEMENTIA; PURIFICATION; RADIOTRACERS; RADIOLIGAND; INHIBITORS; RECEPTORS; TAU;
D O I：
10.1016/j.bmcl.2017.02.019
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (HG-10-102-01) and its precursor (4-((5-chloro-4-(methylamino)pyrimidin-2-yl) amino)-3-hydroxyphenyl)(morpholino)methanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl) amino)-3-[C-11]methoxyphenyl)(morpholino)methanone ([C-11]HG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with [C-11]CH3OTf through O-[C-11]]methylation and isolated by HPLC combined with SPE in 45-55% radiochemical yield, based on [C-11]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110 GBq/mu mol with a total synthesis time of similar to 40-min from EOB. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1351 / 1355
页数：5
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