• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

相似文献

1
Synthesis and in vitro and in vivo evaluation of 18F-labeled positron emission tomography (PET) ligands for imaging the vesicular acetylcholine transporter.用于成像囊泡乙酰胆碱转运体的18F标记正电子发射断层扫描（PET）配体的合成及体内外评价
J Med Chem. 2009 Mar 12;52(5):1358-69. doi: 10.1021/jm8012344.
2
Radiosynthesis and evaluation of a fluorine-18 labeled radioligand targeting vesicular acetylcholine transporter.18F标记的靶向囊泡乙酰胆碱转运体放射性配体的放射性合成与评价
Bioorg Med Chem Lett. 2018 Nov 15;28(21):3425-3430. doi: 10.1016/j.bmcl.2018.09.030. Epub 2018 Sep 24.
3
A new 18F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter.一种用于囊泡乙酰胆碱转运体神经成像的新型18F标记的vesamicol氟乙酰吗啉衍生物。
Nucl Med Biol. 2008 Feb;35(2):185-95. doi: 10.1016/j.nucmedbio.2007.10.004.
4
Heteroaromatic and aniline derivatives of piperidines as potent ligands for vesicular acetylcholine transporter.哌啶的杂芳基和苯胺衍生物作为囊泡型乙酰胆碱转运体的有效配体。
J Med Chem. 2013 Aug 8;56(15):6216-33. doi: 10.1021/jm400664x. Epub 2013 Jul 18.
5
Ex vivo and in vivo evaluation of (2R,3R)-5-[(18)F]-fluoroethoxy- and fluoropropoxy-benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter.作为用于囊泡乙酰胆碱转运体的正电子发射断层显像（PET）放射性配体，（2R,3R）-5-[(18)F]-氟乙氧基和氟丙氧基苯甲酰维司那明的体外和体内评价
Synapse. 2007 Dec;61(12):962-70. doi: 10.1002/syn.20450.
6
Synthesis and biological characterization of a promising F-18 PET tracer for vesicular acetylcholine transporter.一种有前景的用于囊泡乙酰胆碱转运体的F-18正电子发射断层显像（PET）示踪剂的合成及生物学特性研究
Bioorg Med Chem. 2015 Aug 1;23(15):4699-4709. doi: 10.1016/j.bmc.2015.05.058. Epub 2015 Jun 5.
7
Synthesis and evaluation of in vitro bioactivity for vesicular acetylcholine transporter inhibitors containing two carbonyl groups.含有两个羰基的囊泡型乙酰胆碱转运体抑制剂的合成与体外生物活性评价。
Bioorg Med Chem. 2012 Jul 15;20(14):4422-9. doi: 10.1016/j.bmc.2012.05.045. Epub 2012 May 30.
8
Synthesis and evaluation of vesamicol analog (-)-O-[11C]methylvesamicol as a PET ligand for vesicular acetylcholine transporter.囊泡乙酰胆碱转运体PET配体维斯阿米醇类似物（-）-O-[11C]甲基维斯阿米醇的合成与评价
Ann Nucl Med. 2006 Jul;20(6):417-24. doi: 10.1007/BF03027377.
9
Development of novel PET probe [¹¹C](R,R)HAPT and its stereoisomer [¹¹C](S,S)HAPT for vesicular acetylcholine transporter imaging: a PET study in conscious monkey.用于囊泡乙酰胆碱转运体成像的新型正电子发射断层显像（PET）探针[¹¹C](R,R)HAPT及其立体异构体[¹¹C](S,S)HAPT的研发：一项清醒猴的PET研究
Synapse. 2014 Jul;68(7):283-92. doi: 10.1002/syn.21743. Epub 2014 Apr 12.
10
In vitro and in vivo characterization of two C-11-labeled pet tracers for vesicular acetylcholine transporter.两种用于囊泡乙酰胆碱转运体的C-11标记PET示踪剂的体外和体内特性研究
Mol Imaging Biol. 2014 Dec;16(6):773-80. doi: 10.1007/s11307-014-0749-9.

引用本文的文献

1
Radiation dosimetry and fasting-dependent hepatobiliary clearance of the VAChT-specific PET radioligand F-VAT in humans.人类中VAChT特异性PET放射性配体F-VAT的辐射剂量测定及禁食依赖性肝胆清除率
EJNMMI Res. 2025 Jul 7;15(1):83. doi: 10.1186/s13550-025-01273-z.
2
The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review.苯甲酰哌啶片段作为药物化学中的优势结构：全面综述。
Molecules. 2024 Apr 23;29(9):1930. doi: 10.3390/molecules29091930.
3
Computational modeling of PET imaging agents for vesicular acetylcholine transporter (VAChT) protein binding affinity: application of 2D-QSAR modeling and molecular docking techniques.用于囊泡乙酰胆碱转运体（VAChT）蛋白结合亲和力的正电子发射断层扫描（PET）成像剂的计算建模：二维定量构效关系（2D-QSAR）建模和分子对接技术的应用
In Silico Pharmacol. 2023 Apr 4;11(1):9. doi: 10.1007/s40203-023-00146-4. eCollection 2023.
4
In vitro characterization of [H]VAT in cells, animal and human brain tissues for vesicular acetylcholine transporter.用于囊泡乙酰胆碱转运体的 [H]VAT 在细胞、动物和人脑组织中的体外特性。
Eur J Pharmacol. 2021 Nov 15;911:174556. doi: 10.1016/j.ejphar.2021.174556. Epub 2021 Oct 7.
5
Radiosynthesis and evaluation of a fluorine-18 labeled radioligand targeting vesicular acetylcholine transporter.18F标记的靶向囊泡乙酰胆碱转运体放射性配体的放射性合成与评价
Bioorg Med Chem Lett. 2018 Nov 15;28(21):3425-3430. doi: 10.1016/j.bmcl.2018.09.030. Epub 2018 Sep 24.
6
In Vivo and In Vitro Characteristics of Radiolabeled Vesamicol Analogs as the Vesicular Acetylcholine Transporter Imaging Agents.放射性标记的 Vesamicol 类似物作为囊泡乙酰胆碱转运蛋白成像剂的体内和体外特征。
Contrast Media Mol Imaging. 2018 Jun 13;2018:4535476. doi: 10.1155/2018/4535476. eCollection 2018.
7
Kinetic modeling of [ F]VAT, a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non-human primate brain.新型放射性配体[ F]VAT 用于正电子发射断层扫描成像非人类灵长类动物脑的囊泡型乙酰胆碱转运体的动力学建模。
J Neurochem. 2018 Mar;144(6):791-804. doi: 10.1111/jnc.14291. Epub 2018 Mar 25.
8
Synthesis, resolution, and in vitro evaluation of three vesicular acetylcholine transporter ligands and evaluation of the lead fluorine-18 radioligand in a nonhuman primate.三种囊泡型乙酰胆碱转运体配体的合成、拆分及体外评价，以及先导氟-18放射性配体在非人灵长类动物中的评价
Org Biomol Chem. 2017 Jun 21;15(24):5197-5209. doi: 10.1039/c7ob00854f.
9
Kinetics modeling and occupancy studies of a novel C-11 PET tracer for VAChT in nonhuman primates.新型用于非人灵长类动物中囊泡乙酰胆碱转运体（VAChT）的C-11正电子发射断层显像（PET）示踪剂的动力学建模与占有率研究
Nucl Med Biol. 2016 Feb;43(2):131-9. doi: 10.1016/j.nucmedbio.2015.11.003. Epub 2015 Nov 7.
10
Radiation dosimetry of [(18)F]VAT in nonhuman primates.非人灵长类动物中[(18)F]VAT的辐射剂量测定
EJNMMI Res. 2015 Dec;5(1):73. doi: 10.1186/s13550-015-0149-4. Epub 2015 Dec 10.

本文引用的文献

1
Fluorine-18-labeled benzamide analogues for imaging the sigma2 receptor status of solid tumors with positron emission tomography.用于通过正电子发射断层扫描成像实体瘤西格玛2受体状态的氟-18标记苯甲酰胺类似物。
J Med Chem. 2007 Jul 12;50(14):3194-204. doi: 10.1021/jm0614883. Epub 2007 Jun 19.
2
Cholinergic circuits and signaling in the pathophysiology of schizophrenia.胆碱能回路与信号传导在精神分裂症病理生理学中的作用
Int Rev Neurobiol. 2007;78:193-223. doi: 10.1016/S0074-7742(06)78007-2.
3
Safety and efficacy of rivastigmine in adolescents with Down syndrome: a preliminary 20-week, open-label study.卡巴拉汀治疗唐氏综合征青少年的安全性和有效性：一项为期20周的初步开放标签研究。
J Child Adolesc Psychopharmacol. 2006 Dec;16(6):755-65. doi: 10.1089/cap.2006.16.755.
4
Current strategies for the treatment of Alzheimer's disease and other tauopathies.治疗阿尔茨海默病及其他tau蛋白病的当前策略。
Expert Opin Ther Targets. 2006 Oct;10(5):665-76. doi: 10.1517/14728222.10.5.665.
5
Time-dependent cognitive deficits associated with first and second generation antipsychotics: cholinergic dysregulation as a potential mechanism.与第一代和第二代抗精神病药物相关的时间依赖性认知缺陷：胆碱能失调作为一种潜在机制。
J Pharmacol Exp Ther. 2007 Mar;320(3):961-8. doi: 10.1124/jpet.106.106047. Epub 2006 Sep 11.
6
Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition.缺乏囊泡乙酰胆碱转运体的小鼠患有肌无力，并且在物体识别和社交识别方面存在缺陷。
Neuron. 2006 Sep 7;51(5):601-12. doi: 10.1016/j.neuron.2006.08.005.
7
The cholinergic system in Down's syndrome.唐氏综合征中的胆碱能系统。
J Intellect Disabil. 2006 Sep;10(3):261-74. doi: 10.1177/1744629506067615.
8
Synthesis and binding affinities of methylvesamicol analogs for the acetylcholine transporter and sigma receptor.甲基维西酰胺类似物对乙酰胆碱转运体和σ受体的合成及结合亲和力
Bioorg Med Chem. 2006 Apr 15;14(8):2620-6. doi: 10.1016/j.bmc.2005.11.044. Epub 2006 Jan 24.
9
Current pharmacotherapy for Alzheimer's disease.阿尔茨海默病的当前药物治疗方法。
Annu Rev Med. 2006;57:513-33. doi: 10.1146/annurev.med.57.121304.131442.
10
Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease.新型胆碱酯酶抑制剂作为未来治疗阿尔茨海默病的有效药物。
Expert Opin Investig Drugs. 2006 Jan;15(1):1-12. doi: 10.1517/13543784.15.1.1.

用于成像囊泡乙酰胆碱转运体的18F标记正电子发射断层扫描（PET）配体的合成及体内外评价

Synthesis and in vitro and in vivo evaluation of 18F-labeled positron emission tomography (PET) ligands for imaging the vesicular acetylcholine transporter.

作者信息

Tu Zhude, Efange Simon M N, Xu Jinbin, Li Shihong, Jones Lynne A, Parsons Stanley M, Mach Robert H

机构信息

Division of Radiological Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

出版信息

J Med Chem. 2009 Mar 12;52(5):1358-69. doi: 10.1021/jm8012344.

DOI:10.1021/jm8012344
PMID:19203271
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2765529/
Abstract

A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized, and analogues were evaluated in vitro. (+/-)-trans-2-Hydroxy-3-(4-(4-[(18)F]fluorobenzoyl)piperidino)tetralin (9e) has K(i) values of 2.70 nM for VAChT, 191 nM for sigma(1), and 251 nM for sigma(2). The racemic precursor (9d) was resolved via chiral HPLC, and (+/-)-[(18)F]9e, (-)-[(18)F]9e, and (+)-[(18)F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [(18)F]/F(-) and Kryptofix/K(2)CO(3) in DMSO with radiochemical yields of approximately 50-60% and specific activities of >2000 mCi/micromol. (-)-[(18)F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum/cerebellum ratio of 1.88 at 30 min postinjection (p.i.). MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[(18)F]9e in putamen versus cerebellum at 2 h p.i. (-)-[(18)F]9e has potential to be a PET tracer for clinical imaging of the VAChT.

摘要

合成了一类新型的将羰基引入苯并维司米克结构的囊泡型乙酰胆碱转运体抑制剂，并对其类似物进行了体外评估。（±）-反式-2-羟基-3-（4-（4-[(18)F]氟苯甲酰基）哌啶基）四氢萘（9e）对囊泡型乙酰胆碱转运体（VAChT）的K(i)值为2.70 nM，对σ(1)为191 nM，对σ(2)为251 nM。通过手性高效液相色谱法拆分外消旋前体（9d），并通过在二甲基亚砜中用[(18)F]/F(-)和穴状配体/K(2)CO(3)对适当前体进行微波辐照，分别对（±）-[(18)F]9e、（-）-[(18)F]9e和（+）-[(18)F]9e进行放射性标记，放射化学产率约为50-60%，比活度>2000 mCi/μmol。大鼠脑中（-）-[(18)F]9e的摄取与对VAChT的体内选择性一致，注射后30分钟时大鼠纹状体的初始摄取为0.911 %ID/g，纹状体/小脑比值为1.88。猕猴的微型正电子发射断层扫描成像显示，注射后2小时，壳核与小脑中（-）-[(18)F]9e的比值为2.1。（-）-[(18)F]9e有潜力成为用于VAChT临床成像的正电子发射断层扫描示踪剂。