• 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

一系列4-甲氧基-3-(哌啶-4-基)氧基苯甲酰胺作为突触前胆碱转运体新型抑制剂的合成及其构效关系

Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter.

作者信息

Bollinger Sean R, Engers Darren W, Ennis Elizabeth A, Wright Jane, Locuson Charles W, Lindsley Craig W, Blakely Randy D, Hopkins Corey R

机构信息

Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN 37232, USA.

Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

出版信息

Bioorg Med Chem Lett. 2015 Apr 15;25(8):1757-1760. doi: 10.1016/j.bmcl.2015.02.058. Epub 2015 Feb 28.

DOI:10.1016/j.bmcl.2015.02.058
PMID:25801932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4385452/
Abstract

The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold.

摘要

报道了在对MLPCN文库进行高通量筛选后鉴定出的4-甲氧基-3-(哌啶-4-基)苯甲酰胺的合成及构效关系。围绕所报道化合物的3-哌啶取代基以及酰胺官能团对构效关系进行了探索。从最初的先导化合物1-7开始，经过反复的药物化学研究，确定了ML352（10m）。基于类药物骨架，ML352是一种有效的、选择性的胆碱转运体（CHT）抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcab/4385452/090988266112/nihms668568f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcab/4385452/d64fead6fb00/nihms668568f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcab/4385452/090988266112/nihms668568f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcab/4385452/d64fead6fb00/nihms668568f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcab/4385452/090988266112/nihms668568f2.jpg

相似文献

1
Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter.一系列4-甲氧基-3-(哌啶-4-基)氧基苯甲酰胺作为突触前胆碱转运体新型抑制剂的合成及其构效关系
Bioorg Med Chem Lett. 2015 Apr 15;25(8):1757-1760. doi: 10.1016/j.bmcl.2015.02.058. Epub 2015 Feb 28.
2
Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter.ML352的鉴定与特性：一种新型的突触前胆碱转运体非竞争性抑制剂
ACS Chem Neurosci. 2015 Mar 18;6(3):417-27. doi: 10.1021/cn5001809. Epub 2015 Feb 2.
3
Optimization of the choline transporter (CHT) inhibitor ML352: Development of VU6001221, an improved in vivo tool compound.胆碱转运体（CHT）抑制剂ML352的优化：VU6001221的开发，一种改进的体内工具化合物。
Bioorg Med Chem Lett. 2016 Oct 1;26(19):4637-4640. doi: 10.1016/j.bmcl.2016.08.062. Epub 2016 Aug 21.
4
Synthesis and SAR of GlyT1 inhibitors derived from a series of N-((4-(morpholine-4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamides.源自一系列N-((4-(吗啉-4-羰基)-1-(丙基磺酰基)哌啶-4-基)甲基)苯甲酰胺的甘氨酸转运体1（GlyT1）抑制剂的合成与构效关系
Bioorg Med Chem Lett. 2006 Dec 1;16(23):5968-72. doi: 10.1016/j.bmcl.2006.08.131. Epub 2006 Sep 20.
5
Interaction of cis-(6-benzhydrylpiperidin-3-yl)benzylamine analogues with monoamine transporters: structure-activity relationship study of structurally constrained 3,6-disubstituted piperidine analogues of (2,2-diphenylethyl)-[1-(4-fluorobenzyl)piperidin-4-ylmethyl]amine.顺式-（6-二苯甲基哌啶-3-基）苄胺类似物与单胺转运体的相互作用：（2,2-二苯乙基）-[1-（4-氟苄基）哌啶-4-基甲基]胺的结构受限3,6-二取代哌啶类似物的构效关系研究
J Med Chem. 2003 May 22;46(11):2205-15. doi: 10.1021/jm020561w.
6
Design, synthesis, and SAR of N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1.甘氨酸转运蛋白 1 抑制剂的 N-((1-(4-(丙基磺酰基)哌嗪-1-基)环烷基)甲基)苯甲酰胺的设计、合成和 SAR 研究。
Bioorg Med Chem Lett. 2013 Mar 1;23(5):1257-61. doi: 10.1016/j.bmcl.2013.01.006. Epub 2013 Jan 11.
7
Further structurally constrained analogues of cis-(6-benzhydrylpiperidin-3-yl)benzylamine with elucidation of bioactive conformation: discovery of 1,4-diazabicyclo[3.3.1]nonane derivatives and evaluation of their biological properties for the monoamine transporters.顺式-(6-二苯甲基哌啶-3-基)苄胺的进一步结构受限类似物及生物活性构象的阐明：1,4-二氮杂双环[3.3.1]壬烷衍生物的发现及其对单胺转运蛋白的生物学性质评估
J Med Chem. 2004 Oct 7;47(21):5101-13. doi: 10.1021/jm049796t.
8
Design, synthesis, and evaluation of pyrrolo[2,1-f][1,2,4]triazine derivatives as novel hedgehog signaling pathway inhibitors.吡咯并[2,1-f][1,2,4]三嗪衍生物作为新型刺猬信号通路抑制剂的设计、合成与评价
Bioorg Med Chem. 2014 Feb 15;22(4):1429-40. doi: 10.1016/j.bmc.2013.12.055. Epub 2014 Jan 3.
9
Design, synthesis and bioevalution of novel benzamides derivatives as HDAC inhibitors.新型苯甲酰胺衍生物作为组蛋白去乙酰化酶抑制剂的设计、合成与生物评价。
Bioorg Med Chem Lett. 2013 Jan 1;23(1):179-82. doi: 10.1016/j.bmcl.2012.10.114. Epub 2012 Nov 5.
10
Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine.多巴胺转运体高选择性抑制剂的构效关系研究：1-[2-[双(4-氟苯基)甲氧基]乙基]-4-(3-苯基丙基)哌嗪的N-苄基哌啶类似物
J Med Chem. 2003 Apr 10;46(8):1465-9. doi: 10.1021/jm020419v.

引用本文的文献

1
Machine Learning Assisted Hit Prioritization for High Throughput Screening in Drug Discovery.机器学习辅助药物发现高通量筛选中的活性化合物优先级排序
ACS Cent Sci. 2024 Mar 15;10(4):823-832. doi: 10.1021/acscentsci.3c01517. eCollection 2024 Apr 24.

本文引用的文献

1
Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter.ML352的鉴定与特性：一种新型的突触前胆碱转运体非竞争性抑制剂
ACS Chem Neurosci. 2015 Mar 18;6(3):417-27. doi: 10.1021/cn5001809. Epub 2015 Feb 2.
2
Molecular properties of the high-affinity choline transporter CHT1.高亲和力胆碱转运体CHT1的分子特性
J Biochem. 2014 Oct;156(4):181-94. doi: 10.1093/jb/mvu047. Epub 2014 Jul 29.
3
Neuromodulation by acetylcholine: examples from schizophrenia and depression.
乙酰胆碱介导的神经调节：来自精神分裂症和抑郁症的实例
Curr Opin Neurobiol. 2014 Dec;29:88-95. doi: 10.1016/j.conb.2014.06.004. Epub 2014 Jun 28.
4
Defective presynaptic choline transport underlies hereditary motor neuropathy.遗传性运动神经病的根本原因是突触前胆碱转运缺陷。
Am J Hum Genet. 2012 Dec 7;91(6):1103-7. doi: 10.1016/j.ajhg.2012.09.019. Epub 2012 Nov 8.
5
Nonoisotopic assay for the presynaptic choline transporter reveals capacity for allosteric modulation of choline uptake.非同位素分析法测定突触前胆碱转运体，揭示了对胆碱摄取的变构调节能力。
ACS Chem Neurosci. 2012 Oct 17;3(10):767-81. doi: 10.1021/cn3000718. Epub 2012 Jul 9.
6
Choline transporter gene variation is associated with attention-deficit hyperactivity disorder.胆碱转运体基因变异与注意缺陷多动障碍有关。
J Neurodev Disord. 2009 Dec;1(4):252-63. doi: 10.1007/s11689-009-9033-8. Epub 2009 Aug 28.
7
Polymorphic variation in choline transporter gene (CHT1) is associated with early, subclinical measures of carotid atherosclerosis in humans.胆碱转运体基因（CHT1）的多态性变异与人类颈动脉粥样硬化的早期亚临床指标相关。
Int J Cardiovasc Imaging. 2012 Feb;28(2):243-50. doi: 10.1007/s10554-011-9831-4. Epub 2011 Feb 20.
8
Multivariate permutation analysis associates multiple polymorphisms with subphenotypes of major depression.多变量排列分析将多种多态性与重度抑郁症的亚表型联系起来。
Genes Brain Behav. 2008 Jun;7(4):487-95. doi: 10.1111/j.1601-183X.2007.00384.x. Epub 2007 Dec 6.
9
Na+, Cl-, and pH dependence of the human choline transporter (hCHT) in Xenopus oocytes: the proton inactivation hypothesis of hCHT in synaptic vesicles.非洲爪蟾卵母细胞中人类胆碱转运体（hCHT）对Na⁺、Cl⁻和pH的依赖性：突触小泡中hCHT的质子失活假说
J Neurosci. 2006 Sep 27;26(39):9851-9. doi: 10.1523/JNEUROSCI.1862-06.2006.
10
The Caenorhabditis elegans choline transporter CHO-1 sustains acetylcholine synthesis and motor function in an activity-dependent manner.秀丽隐杆线虫胆碱转运体CHO-1以活动依赖的方式维持乙酰胆碱的合成和运动功能。
J Neurosci. 2006 Jun 7;26(23):6200-12. doi: 10.1523/JNEUROSCI.5036-05.2006.