• 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

新型抗氧化和神经保护多靶点导向配体的设计、合成与生物评价，该配体能阻断钙通道。

Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels.

机构信息

Neurosciences Intégratives et Cliniques EA 481, Pôle de Chimie Organique et Thérapeutique, Univ. Bourgogne Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, France.

PEPITE EA4267, Laboratoire de Toxicologie Cellulaire, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.

出版信息

Molecules. 2020 Mar 14;25(6):1329. doi: 10.3390/molecules25061329.

DOI:10.3390/molecules25061329
PMID:32183349
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7144121/
Abstract

We report herein the design, synthesis and biological evaluation of new antioxidant and neuroprotective multitarget directed ligands (MTDLs) able to block Ca channels. New dialkyl 2,6-dimethyl-4-(4-(prop-2-yn-1-yloxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate MTDLs -, resulting from the juxtaposition of nimodipine, a Ca channel antagonist, and rasagiline, a known MAO inhibitor, have been obtained from appropriate and commercially available precursors using a Hantzsch reaction. Pertinent biological analysis has prompted us to identify the MTDL 3,5-dimethyl-2,6-dimethyl-4-[4-(prop-2-yn-1-yloxy)phenyl]-1,4-dihydro- pyridine- 3,5-dicarboxylate (), as an attractive antioxidant (1.75 TE), Ca channel antagonist (46.95% at 10 μM), showing significant neuroprotection (38%) against HO at 10 μM, being considered thus a hit-compound for further investigation in our search for anti-Alzheimer's disease agents.

摘要

我们在此报告了新的抗氧化和神经保护多靶点定向配体（MTDL）的设计、合成和生物学评价，这些配体能够阻断 Ca 通道。新的二烷基 2,6-二甲基-4-（4-（丙炔-1-氧基）苯基）-1,4-二氢吡啶-3,5-二甲酸酯 MTDL-，是将钙通道拮抗剂尼莫地平与已知的 MAO 抑制剂雷沙吉兰并置而成，通过适当的和商业可得的前体，使用 Hantzsch 反应得到。相关的生物学分析促使我们鉴定出 MTDL 3,5-二甲基-2,6-二甲基-4-[4-（丙炔-1-氧基）苯基]-1,4-二氢吡啶-3,5-二甲酸酯（）作为一种有吸引力的抗氧化剂（1.75 TE）、Ca 通道拮抗剂（在 10 μM 时为 46.95%），对 HO 具有显著的神经保护作用（在 10 μM 时为 38%），因此被认为是我们寻找抗阿尔茨海默病药物的进一步研究的命中化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b2b51c3858c0/molecules-25-01329-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/e2fdb92a1a46/molecules-25-01329-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/66337866e98b/molecules-25-01329-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/24d21dd16b89/molecules-25-01329-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b45c2029c12e/molecules-25-01329-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/2240ed9de9e0/molecules-25-01329-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/80f7b90815df/molecules-25-01329-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/62f8d6f49350/molecules-25-01329-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b27907158cca/molecules-25-01329-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/1845a72553de/molecules-25-01329-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b4458d598e6f/molecules-25-01329-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/64ef56e8e4e4/molecules-25-01329-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/ade8c7f0492c/molecules-25-01329-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/85d3695651af/molecules-25-01329-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/c3b802b015a9/molecules-25-01329-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b6a1d9b27b39/molecules-25-01329-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/22b1c143bac9/molecules-25-01329-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/6e1e39c4982c/molecules-25-01329-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b2b51c3858c0/molecules-25-01329-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/e2fdb92a1a46/molecules-25-01329-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/66337866e98b/molecules-25-01329-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/24d21dd16b89/molecules-25-01329-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b45c2029c12e/molecules-25-01329-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/2240ed9de9e0/molecules-25-01329-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/80f7b90815df/molecules-25-01329-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/62f8d6f49350/molecules-25-01329-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b27907158cca/molecules-25-01329-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/1845a72553de/molecules-25-01329-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b4458d598e6f/molecules-25-01329-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/64ef56e8e4e4/molecules-25-01329-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/ade8c7f0492c/molecules-25-01329-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/85d3695651af/molecules-25-01329-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/c3b802b015a9/molecules-25-01329-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b6a1d9b27b39/molecules-25-01329-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/22b1c143bac9/molecules-25-01329-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/6e1e39c4982c/molecules-25-01329-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/328f/7144121/b2b51c3858c0/molecules-25-01329-g017.jpg

相似文献

1
Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels.新型抗氧化和神经保护多靶点导向配体的设计、合成与生物评价，该配体能阻断钙通道。
Molecules. 2020 Mar 14;25(6):1329. doi: 10.3390/molecules25061329.
2
Synthesis of Hantzsch Adducts as Cholinesterases and Calcium Flux inhibitors, Antioxidants and Neuroprotectives.作为乙酰胆碱酯酶和钙通量抑制剂、抗氧化剂和神经保护剂的 Hantzsch 加合物的合成。
Int J Mol Sci. 2020 Oct 16;21(20):7652. doi: 10.3390/ijms21207652.
3
Multi-target 1,4-dihydropyridines showing calcium channel blockade and antioxidant capacity for Alzheimer's disease therapy.具有钙通道阻滞和抗氧化能力的多靶点 1,4-二氢吡啶类化合物，用于治疗阿尔茨海默病。
Bioorg Chem. 2019 Oct;91:103205. doi: 10.1016/j.bioorg.2019.103205. Epub 2019 Aug 16.
4
A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer's Disease.丹曲林钠作为阿尔茨海默病多靶药物的前瞻性再利用。
Molecules. 2019 Nov 25;24(23):4298. doi: 10.3390/molecules24234298.
5
Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer's disease.他克林吡啶类化合物，首批他克林 - 二氢吡啶杂合物，作为用于治疗阿尔茨海默病的多靶点导向配体。
J Med Chem. 2009 May 14;52(9):2724-32. doi: 10.1021/jm801292b.
6
Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer's disease.新型多能他克林-二氢吡啶杂化物具有改善的乙酰胆碱酯酶抑制和神经保护活性，作为治疗阿尔茨海默病的潜在药物。
J Med Chem. 2006 Dec 28;49(26):7607-10. doi: 10.1021/jm061047j.
7
Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease Treatment.探索磺胺-二氢吡啶杂合体作为阿尔茨海默病治疗多靶点配体的潜力。
Int J Mol Sci. 2023 Jun 4;24(11):9742. doi: 10.3390/ijms24119742.
8
Polycyclic propargylamine and acetylene derivatives as multifunctional neuroprotective agents.多环丙炔胺和乙炔衍生物作为多功能神经保护剂。
Eur J Med Chem. 2014 Jun 10;80:122-34. doi: 10.1016/j.ejmech.2014.04.039. Epub 2014 Apr 13.
9
(±)-: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3β Inhibition with Calcium Channel Antagonism and Antiaggregating Properties for Alzheimer's Disease.(±)-：Pentatarget-导向配体，兼具胆碱酯酶、单胺氧化酶和糖原合成酶激酶 3β抑制作用，以及钙通道拮抗和抗聚集作用，可用于治疗阿尔茨海默病。
ACS Chem Neurosci. 2021 Apr 21;12(8):1328-1342. doi: 10.1021/acschemneuro.0c00803. Epub 2021 Apr 2.
10
Substituent effect of N-benzylated gramine derivatives that prevent the PP2A inhibition and dissipate the neuronal Ca overload, as a multitarget strategy for the treatment of Alzheimer's disease.N-苯甲酰化麦角碱衍生物的取代基效应可防止蛋白磷酸酶 2A 抑制和消除神经元钙超载，是治疗阿尔茨海默病的多靶点策略。
Bioorg Med Chem. 2018 May 15;26(9):2551-2560. doi: 10.1016/j.bmc.2018.04.019. Epub 2018 Apr 9.

引用本文的文献

1
Updates on Intrinsic Medicinal Chemistry of 1,4-dihydropyridines, Perspectives on Synthesis and Pharmacokinetics of Novel 1,4-dihydropyrimidines as Calcium Channel Blockers: Clinical Pharmacology.1,4 - 二氢吡啶的内在药物化学进展，新型1,4 - 二氢嘧啶作为钙通道阻滞剂的合成与药代动力学展望：临床药理学
Curr Top Med Chem. 2025 Jan 1. doi: 10.2174/0115680266323908241114064318.
2
Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease Treatment.探索磺胺-二氢吡啶杂合体作为阿尔茨海默病治疗多靶点配体的潜力。
Int J Mol Sci. 2023 Jun 4;24(11):9742. doi: 10.3390/ijms24119742.
3

本文引用的文献

1
New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition.新型双重小分子阿尔茨海默病治疗药物，兼具组胺 H 受体（H3R）拮抗作用、钙通道阻断作用以及额外的胆碱酯酶抑制作用。
J Med Chem. 2019 Dec 26;62(24):11416-11422. doi: 10.1021/acs.jmedchem.9b00937. Epub 2019 Dec 5.
2
Combined Treatment with Three Natural Antioxidants Enhances Neuroprotection in a SH-SY5Y 3D Culture Model.三种天然抗氧化剂联合治疗增强SH-SY5Y三维培养模型中的神经保护作用。
Antioxidants (Basel). 2019 Sep 20;8(10):420. doi: 10.3390/antiox8100420.
3
Synthesis of Dihydropyrimidines: Isosteres of Nifedipine and Evaluation of Their Calcium Channel Blocking Efficiency.
二氢嘧啶的合成：硝苯地平的等排体及其钙通道阻滞效率的评价。
Molecules. 2023 Jan 12;28(2):784. doi: 10.3390/molecules28020784.
4
Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation.Biginelli 反应合成具有钙通道阻断能力、胆碱酯酶抑制作用、抗氧化能力和 Nrf2 激活作用的新型多靶点导向配体。
Molecules. 2022 Dec 22;28(1):71. doi: 10.3390/molecules28010071.
5
Synthesis of Hantzsch Adducts as Cholinesterases and Calcium Flux inhibitors, Antioxidants and Neuroprotectives.作为乙酰胆碱酯酶和钙通量抑制剂、抗氧化剂和神经保护剂的 Hantzsch 加合物的合成。
Int J Mol Sci. 2020 Oct 16;21(20):7652. doi: 10.3390/ijms21207652.
Multi-target 1,4-dihydropyridines showing calcium channel blockade and antioxidant capacity for Alzheimer's disease therapy.
具有钙通道阻滞和抗氧化能力的多靶点 1,4-二氢吡啶类化合物，用于治疗阿尔茨海默病。
Bioorg Chem. 2019 Oct;91:103205. doi: 10.1016/j.bioorg.2019.103205. Epub 2019 Aug 16.
4
Tau-Centric Multitarget Approach for Alzheimer's Disease: Development of First-in-Class Dual Glycogen Synthase Kinase 3β and Tau-Aggregation Inhibitors.以 Tau 为中心的阿尔茨海默病多靶点方法：首创双糖原合酶激酶 3β 和 Tau 聚集抑制剂的开发。
J Med Chem. 2018 Sep 13;61(17):7640-7656. doi: 10.1021/acs.jmedchem.8b00610. Epub 2018 Aug 24.
5
Tacripyrimidines, the first tacrine-dihydropyrimidine hybrids, as multi-target-directed ligands for Alzheimer's disease.他克林-二氢嘧啶类化合物，作为阿尔茨海默病的多靶点导向配体的第一个他克林-二氢嘧啶类混合物。
Eur J Med Chem. 2018 Jul 15;155:839-846. doi: 10.1016/j.ejmech.2018.06.044. Epub 2018 Jun 19.
6
Synthesis, Biological Evaluation and Molecular Modeling Studies of Propargyl-Containing 2,4,6-Trisubstituted Pyrimidine Derivatives as Potential Anti-Parkinson Agents.含炔丙基的 2,4,6-三取代嘧啶衍生物的合成、生物评价及分子模拟研究作为潜在的抗帕金森药物。
ChemMedChem. 2018 Apr 6;13(7):705-712. doi: 10.1002/cmdc.201700589. Epub 2018 Mar 13.
7
Alzheimer's Disease, the "One-Molecule, One-Target" Paradigm, and the Multitarget Directed Ligand Approach.阿尔茨海默病、"一个分子，一个靶点"范式与多靶点导向配体方法。
ACS Chem Neurosci. 2018 Mar 21;9(3):401-403. doi: 10.1021/acschemneuro.8b00069. Epub 2018 Feb 21.
8
Multicomponent Reactions for Multitargeted Compounds for Alzheimer`s Disease.用于治疗阿尔茨海默病的多靶点化合物的多组分反应
Curr Top Med Chem. 2017;17(31):3319-3327. doi: 10.2174/1568026618666180112155424.
9
The Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators.抗氧化添加剂治疗阿尔茨海默病的方法：新型阿魏酸（硫辛酸）加褪黑素修饰他克林作为胆碱酯酶抑制剂、直接抗氧化剂和核因子（红细胞衍生 2）样 2 激活剂。
J Med Chem. 2016 Nov 10;59(21):9967-9973. doi: 10.1021/acs.jmedchem.6b01178. Epub 2016 Oct 31.
10
Multitarget compounds bearing tacrine- and donepezil-like structural and functional motifs for the potential treatment of Alzheimer's disease.具有他克林和多奈哌齐样结构和功能基序的多靶化合物，用于治疗阿尔茨海默病的潜在药物。
Prog Neurobiol. 2017 Apr;151:4-34. doi: 10.1016/j.pneurobio.2015.12.003. Epub 2016 Jan 18.