• 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

1-(1-(苯并[b]噻吩-2-基)环己基)哌啶（BTCP）类似物作为锥虫硫醇还原酶抑制剂的合成与评价

Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase.

作者信息

Patterson Stephen, Jones Deuan C, Shanks Emma J, Frearson Julie A, Gilbert Ian H, Wyatt Paul G, Fairlamb Alan H

机构信息

Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

出版信息

ChemMedChem. 2009 Aug;4(8):1341-53. doi: 10.1002/cmdc.200900098.

DOI:10.1002/cmdc.200900098
PMID:19557802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2929374/
Abstract

Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (K(i)=1 microM) and biologically active against bloodstream T. brucei (EC(50)=10 microM), but with poor selectivity against mammalian MRC5 cells (EC(50)=29 microM). Analogues with improved enzymatic and biological activity were obtained. The structure-activity relationships of this novel series are discussed.

摘要

合成了32种苯环利定类似物，并将其作为锥虫硫醇还原酶（TryR）的抑制剂进行测试，TryR是锥虫和利什曼原虫寄生虫中的一个潜在药物靶点。发现先导化合物BTCP（1,1-(1-苯并[b]噻吩-2-基-环己基)哌啶）是该酶的竞争性抑制剂（K(i)=1微摩尔），对布氏锥虫血流型具有生物活性（EC(50)=10微摩尔），但对哺乳动物MRC5细胞的选择性较差（EC(50)=29微摩尔）。获得了具有改善的酶活性和生物活性的类似物。讨论了该新系列的构效关系

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/131ebbfa49da/cmdc0004-1341-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/b2a24dc15b39/cmdc0004-1341-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/3c64a519e035/cmdc0004-1341-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/d743d4029554/cmdc0004-1341-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/0c87615dee02/cmdc0004-1341-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/059b31ab9845/cmdc0004-1341-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/b828cb521b96/cmdc0004-1341-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/131ebbfa49da/cmdc0004-1341-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/b2a24dc15b39/cmdc0004-1341-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/3c64a519e035/cmdc0004-1341-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/d743d4029554/cmdc0004-1341-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/0c87615dee02/cmdc0004-1341-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/059b31ab9845/cmdc0004-1341-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/b828cb521b96/cmdc0004-1341-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dc/2929374/131ebbfa49da/cmdc0004-1341-f3.jpg

相似文献

1
Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase.1-(1-(苯并[b]噻吩-2-基)环己基)哌啶（BTCP）类似物作为锥虫硫醇还原酶抑制剂的合成与评价
ChemMedChem. 2009 Aug;4(8):1341-53. doi: 10.1002/cmdc.200900098.
2
Improved tricyclic inhibitors of trypanothione reductase by screening and chemical synthesis.通过筛选和化学合成改进的锥虫硫醇还原酶三环抑制剂
ChemMedChem. 2009 Aug;4(8):1333-40. doi: 10.1002/cmdc.200900097.
3
Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents.带有N-(3-苯丙基)取代基的多胺是有效的锥虫硫醇还原酶竞争性抑制剂和杀锥虫剂。
Bioorg Med Chem Lett. 2001 Jan 22;11(2):251-4. doi: 10.1016/s0960-894x(00)00643-0.
4
Investigation of trypanothione reductase as a drug target in Trypanosoma brucei.对布氏锥虫中的硫醇还原酶作为药物靶点的研究。
ChemMedChem. 2009 Dec;4(12):2060-9. doi: 10.1002/cmdc.200900262.
5
Ebsulfur is a benzisothiazolone cytocidal inhibitor targeting the trypanothione reductase of Trypanosoma brucei.埃布斯氟素是一种苯并异噻唑啉细胞毒素抑制剂，靶向布氏锥虫的硫醇还原酶。
J Biol Chem. 2013 Sep 20;288(38):27456-27468. doi: 10.1074/jbc.M113.495101. Epub 2013 Jul 29.
6
Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.二氢喹唑啉类化合物作为一种新型的布氏锥虫硫醇还原酶抑制剂：通过蛋白质晶体学发现、合成及结合模式表征。
J Med Chem. 2011 Oct 13;54(19):6514-30. doi: 10.1021/jm200312v. Epub 2011 Sep 1.
7
Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs.作为潜在抗锥虫和抗利什曼原虫药物的锥虫硫醇还原酶的吩噻嗪抑制剂。
J Med Chem. 1998 Jan 15;41(2):148-56. doi: 10.1021/jm960814j.
8
Time-dependent inhibitors of trypanothione reductase: analogues of the spermidine alkaloid lunarine and related natural products.依时性锥虫硫醇还原酶抑制剂：亚精胺生物碱鲁纳灵及其相关天然产物的类似物
Bioorg Med Chem. 2006 Apr 1;14(7):2266-78. doi: 10.1016/j.bmc.2005.11.004. Epub 2005 Nov 21.
9
Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione synthetase inhibitors.设计、合成及生物评价抗布氏锥虫硫醇合成酶抑制剂。
ChemMedChem. 2012 Jan 2;7(1):95-106. doi: 10.1002/cmdc.201100420. Epub 2011 Dec 8.
10
Synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates.多胺-羟基苯并三唑缀合物的合成及其体外抗动质体活性
Bioorg Med Chem. 2017 Jan 1;25(1):84-90. doi: 10.1016/j.bmc.2016.10.013. Epub 2016 Oct 12.

引用本文的文献

1
Targeting Trypanothione Synthetase and Trypanothione Reductase: Development of Common Inhibitors to Tackle Trypanosomatid Disease.靶向 trypanothione 合成酶和 trypanothione 还原酶：开发用于治疗锥虫病的通用抑制剂
Pharmaceuticals (Basel). 2025 Aug 11;18(8):1182. doi: 10.3390/ph18081182.
2
Targeting Trypanothione Metabolism in Trypanosomatids.靶向原虫的硫醇代谢。
Molecules. 2024 May 9;29(10):2214. doi: 10.3390/molecules29102214.
3
Antileishmanial Activities of ()-2-(Nitroimidazolylmethylene)-3()-Benzofuranones: Synthesis, Assessment, and Bioactivation by NTR 1 and 2.

本文引用的文献

1
Improved tricyclic inhibitors of trypanothione reductase by screening and chemical synthesis.通过筛选和化学合成改进的锥虫硫醇还原酶三环抑制剂
ChemMedChem. 2009 Aug;4(8):1333-40. doi: 10.1002/cmdc.200900097.
2
A comparative study of methylglyoxal metabolism in trypanosomatids.锥虫体内甲基乙二醛代谢的比较研究。
FEBS J. 2009 Jan;276(2):376-86. doi: 10.1111/j.1742-4658.2008.06788.x. Epub 2008 Dec 3.
3
Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities.
（）-2-（硝基咪唑基亚甲基）-3-（苯并呋喃酮）的抗利什曼原虫活性：合成、评估和 NTR1 和 NTR2 的生物激活作用。
Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0058322. doi: 10.1128/aac.00583-22. Epub 2022 Oct 26.
4
An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases.针对动基体原生动物感染的基于靶点的药物设计概述：人类非洲锥虫病、恰加斯病和利什曼病
Molecules. 2021 Jul 30;26(15):4629. doi: 10.3390/molecules26154629.
5
Targeting Trypanothione Reductase, a Key Enzyme in the Redox Trypanosomatid Metabolism, to Develop New Drugs against Leishmaniasis and Trypanosomiases.针对氧化还原原生动物代谢中的关键酶——硫醇还原酶，开发治疗利什曼病和锥虫病的新药。
Molecules. 2020 Apr 21;25(8):1924. doi: 10.3390/molecules25081924.
6
Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase.ML251的鉴定，一种布氏锥虫和克氏锥虫磷酸果糖激酶的强效抑制剂。
ACS Med Chem Lett. 2013 Oct 30;5(1):12-7. doi: 10.1021/ml400259d. eCollection 2014 Jan 9.
7
Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.二氢喹唑啉类化合物作为一种新型的布氏锥虫硫醇还原酶抑制剂：通过蛋白质晶体学发现、合成及结合模式表征。
J Med Chem. 2011 Oct 13;54(19):6514-30. doi: 10.1021/jm200312v. Epub 2011 Sep 1.
8
State of the art in African trypanosome drug discovery.非洲锥虫药物发现的最新进展。
Curr Top Med Chem. 2011;11(10):1255-74. doi: 10.2174/156802611795429167.
9
Synthesis and evaluation of indatraline-based inhibitors for trypanothione reductase.吲达胺类硫醇还原酶抑制剂的合成与评价。
ChemMedChem. 2011 Feb 7;6(2):321-8. doi: 10.1002/cmdc.201000442. Epub 2010 Dec 15.
10
N-myristoyltransferase inhibitors as new leads to treat sleeping sickness.N-豆蔻酰转移酶抑制剂作为治疗昏睡病的新先导。
Nature. 2010 Apr 1;464(7289):728-32. doi: 10.1038/nature08893.
基于二芳基硫醚的锥虫硫醇还原酶抑制剂：抑制效力、修正的结合模式及抗原虫活性
Org Biomol Chem. 2008 Nov 7;6(21):3935-47. doi: 10.1039/b806371k. Epub 2008 Sep 9.
4
Kinetoplastids: related protozoan pathogens, different diseases.动质体目：相关的原生动物病原体，引发不同疾病。
J Clin Invest. 2008 Apr;118(4):1301-10. doi: 10.1172/JCI33945.
5
High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity.高通量筛选提供了具有抗锥虫活性的新型选择性锥虫硫醇还原酶抑制剂。
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1280-3. doi: 10.1016/j.bmcl.2006.12.016. Epub 2006 Dec 9.
6
Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening.通过高通量筛选发现2-亚氨基苯并咪唑作为一类新型的锥虫硫醇还原酶抑制剂。
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1422-7. doi: 10.1016/j.bmcl.2006.11.090. Epub 2006 Dec 3.
7
Innovative lead discovery strategies for tropical diseases.热带疾病的创新先导化合物发现策略。
Nat Rev Drug Discov. 2006 Nov;5(11):941-55. doi: 10.1038/nrd2144.
8
Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class of trypanothione reductase inhibitor, and of N-acyl derivatives of 2-amino-4-chlorophenyl phenyl sulfide.新型锥虫硫醇还原酶抑制剂——季铵芳基烷基铵2-氨基-4-氯苯基苯硫醚及其N-酰基衍生物的抗锥虫、抗利什曼原虫和抗疟活性
J Med Chem. 2005 Dec 15;48(25):8087-97. doi: 10.1021/jm050819t.
9
Time-dependent inhibitors of trypanothione reductase: analogues of the spermidine alkaloid lunarine and related natural products.依时性锥虫硫醇还原酶抑制剂：亚精胺生物碱鲁纳灵及其相关天然产物的类似物
Bioorg Med Chem. 2006 Apr 1;14(7):2266-78. doi: 10.1016/j.bmc.2005.11.004. Epub 2005 Nov 21.
10
Mechanism and structure-activity relationships of norspermidine-based peptidic inhibitors of trypanothione reductase.基于 norspermidine 的锥虫硫醇还原酶肽类抑制剂的作用机制及构效关系
Bioorg Med Chem. 2005 Jul 15;13(14):4513-26. doi: 10.1016/j.bmc.2005.04.039.