کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10583694 | 981298 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis and evaluation of a 18F-labeled spirocyclic piperidine derivative as promising Ï1 receptor imaging agent
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
Several spirocyclic piperidine derivatives were designed and synthesized as Ï1 receptor ligands. In vitro competition binding assays showed that the fluoroalkoxy analogues with small substituents possessed high affinity towards Ï1 receptors and subtype selectivity. Particularly for ligand 1â²-((6-(2-fluoroethoxy)pyridin-3-yl)methyl)-3H-spiro[2-benzofuran-1,4â²-piperidine] (2), high Ï1 receptor affinity (Ki = 2.30 nM) and high Ï1/Ï2 subtype selectivity (142-fold) as well as high Ï1/VAChT selectivity (234-fold) were observed. [18F]2 was synthesized using an efficient one-pot, two-step reaction method in a home-made automated synthesis module, with an overall isolated radiochemical yield of 8-10%, a radiochemical purity of higher than 99%, and specific activity of 56-78 GBq/μmol. Biodistribution studies of [18F]2 in ICR mice indicated high initial brain uptake and a relatively fast washout. Administration of haloperidol, compound 1 and different concentrations of SA4503 (3, 5, or 10 μmol/kg) 5 min prior to injection of [18F]2 significantly decreased the accumulation of radiotracer in organs known to contain Ï1 receptors. Ex vivo autoradiography in Sprague-Dawley rats demonstrated high accumulation of radiotracer in brain areas with high expression of Ï1 receptors. These encouraging results prove that [18F]2 is a suitable candidate for Ï1 receptor imaging with PET in humans.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 19, 1 October 2014, Pages 5270-5278
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 19, 1 October 2014, Pages 5270-5278
نویسندگان
Yuan-Yuan Chen, Xia Wang, Jin-Ming Zhang, Winnie Deuther-Conrad, Xiao-Jun Zhang, Yiyun Huang, Yan Li, Jia-Jun Ye, Meng-Chao Cui, Jörg Steinbach, Peter Brust, Bo-Li Liu, Hong-Mei Jia,