• 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

发现 N-(苯并[1,2,3]三唑-1-基)-N-(苄基)乙酰胺基)苯基)羧酰胺作为严重急性呼吸综合征冠状病毒 (SARS-CoV) 3CLpro 抑制剂：鉴定出 ML300 和非共价纳米摩尔抑制剂，具有诱导契合结合。

Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.

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.

出版信息

Bioorg Med Chem Lett. 2013 Nov 15;23(22):6172-7. doi: 10.1016/j.bmcl.2013.08.112. Epub 2013 Sep 7.

DOI:10.1016/j.bmcl.2013.08.112
PMID:24080461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3878165/
Abstract

Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond.

摘要

在此，我们报告了通过美国国立卫生研究院分子库探针生产中心网络（MLPCN）发现和 SAR 的新型 SARS-CoV 3CLpro 抑制剂系列。除了 ML188，ML300 代表了来自该合作的第二个针对 3CLpro 的探针。与 SARS-CoV 3CLpro 结合的 ML300 类似物的 X 射线结构突出显示了 S2-S4 结合口袋的独特诱导契合重排，导致首次保留单个酰胺键的亚微米级非共价 3CLpro 抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/f3df8accffd3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/f45abfb46102/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/7d5b0213a757/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/ba35bd7f5ad0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/fdf4d7e2ac83/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/42e6aa8093ca/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/aee4d4ac9162/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/ab3f3c2d4325/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/75c3f8c27d79/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/42e208426527/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/ce8f9eedd707/fx2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/f3df8accffd3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/f45abfb46102/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/7d5b0213a757/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/ba35bd7f5ad0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/fdf4d7e2ac83/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/42e6aa8093ca/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/aee4d4ac9162/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/ab3f3c2d4325/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/75c3f8c27d79/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/42e208426527/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/ce8f9eedd707/fx2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/7126719/f3df8accffd3/gr6.jpg

相似文献

1
Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.发现 N-(苯并[1,2,3]三唑-1-基)-N-(苄基)乙酰胺基)苯基)羧酰胺作为严重急性呼吸综合征冠状病毒 (SARS-CoV) 3CLpro 抑制剂：鉴定出 ML300 和非共价纳米摩尔抑制剂，具有诱导契合结合。
Bioorg Med Chem Lett. 2013 Nov 15;23(22):6172-7. doi: 10.1016/j.bmcl.2013.08.112. Epub 2013 Sep 7.
2
Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease.发现、合成及基于结构的优化一系列 N-(叔丁基)-2-(N-芳基氨基)-2-(吡啶-3-基)乙酰胺（ML188），作为强效非共价小分子抑制剂，针对严重急性呼吸综合征冠状病毒（SARS-CoV）3CL 蛋白酶。
J Med Chem. 2013 Jan 24;56(2):534-46. doi: 10.1021/jm301580n. Epub 2013 Jan 3.
3
Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CL).基于结构的 ML300 衍生非共价抑制剂对严重急性呼吸综合征冠状病毒 3CL 蛋白酶（SARS-CoV-2 3CL）的优化。
J Med Chem. 2022 Feb 24;65(4):2880-2904. doi: 10.1021/acs.jmedchem.1c00598. Epub 2021 Aug 4.
4
Inhibition of SARS-CoV 3CL protease by flavonoids.黄酮类化合物对 SARS-CoV 3CL 蛋白酶的抑制作用。
J Enzyme Inhib Med Chem. 2020 Dec;35(1):145-151. doi: 10.1080/14756366.2019.1690480.
5
Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors.肽模拟物严重急性呼吸综合征类胰凝乳蛋白酶样蛋白酶抑制剂的设计与合成
J Med Chem. 2005 Nov 3;48(22):6767-71. doi: 10.1021/jm050548m.
6
Synthetic and computational efforts towards the development of peptidomimetics and small-molecule SARS-CoV 3CLpro inhibitors.针对肽模拟物和小分子 SARS-CoV 3CLpro 抑制剂的合成和计算研究。
Bioorg Med Chem. 2021 Sep 15;46:116301. doi: 10.1016/j.bmc.2021.116301. Epub 2021 Jul 3.
7
Synthesis of novel test compounds for antiviral chemotherapy of severe acute respiratory syndrome (SARS).用于严重急性呼吸综合征（SARS）抗病毒化疗的新型测试化合物的合成。
Curr Med Chem. 2005;12(18):2095-162. doi: 10.2174/0929867054637644.
8
Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors.发现并优化 2-((1H-吲哚-3-基)硫代)-N-苄基-乙酰胺类化合物作为新型 SARS-CoV-2 RdRp 抑制剂。
Eur J Med Chem. 2021 Nov 5;223:113622. doi: 10.1016/j.ejmech.2021.113622. Epub 2021 Jun 10.
9
Broad-spectrum coronavirus antiviral drug discovery.广谱冠状病毒抗病毒药物的发现。
Expert Opin Drug Discov. 2019 Apr;14(4):397-412. doi: 10.1080/17460441.2019.1581171. Epub 2019 Mar 8.
10
Substrate specificity profiling and identification of a new class of inhibitor for the major protease of the SARS coronavirus.严重急性呼吸综合征冠状病毒主要蛋白酶的底物特异性分析及新型抑制剂的鉴定
Biochemistry. 2007 Jul 31;46(30):8744-52. doi: 10.1021/bi0621415. Epub 2007 Jul 3.

引用本文的文献

1
Prediction of enzyme inhibition (IC) using a combination of protein-ligand docking and semiempirical quantum mechanics.结合蛋白质-配体对接和半经验量子力学预测酶抑制作用（IC）
J Mol Model. 2025 Jul 12;31(8):209. doi: 10.1007/s00894-025-06423-7.
2
Alchemical Enhanced Sampling with Optimized Phase Space Overlap.具有优化相空间重叠的炼金术增强采样
J Chem Theory Comput. 2024 May 14;20(9):3935-3953. doi: 10.1021/acs.jctc.4c00251. Epub 2024 Apr 26.
3
On the origins of SARS-CoV-2 main protease inhibitors.关于严重急性呼吸综合征冠状病毒2主要蛋白酶抑制剂的起源

本文引用的文献

1
Intervention strategies for emerging viruses: use of antivirals.新兴病毒的干预策略：抗病毒药物的使用。
Curr Opin Virol. 2013 Apr;3(2):217-24. doi: 10.1016/j.coviro.2013.03.001. Epub 2013 Apr 4.
2
Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease.发现、合成及基于结构的优化一系列 N-(叔丁基)-2-(N-芳基氨基)-2-(吡啶-3-基)乙酰胺（ML188），作为强效非共价小分子抑制剂，针对严重急性呼吸综合征冠状病毒（SARS-CoV）3CL 蛋白酶。
J Med Chem. 2013 Jan 24;56(2):534-46. doi: 10.1021/jm301580n. Epub 2013 Jan 3.
3
RSC Med Chem. 2023 Oct 13;15(1):81-118. doi: 10.1039/d3md00493g. eCollection 2024 Jan 25.
4
[Not Available].[无可用内容]
Acta Pharm Sin B. 2024 Jan;14(1):87-109. doi: 10.1016/j.apsb.2023.08.004. Epub 2023 Aug 9.
5
Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2.主蛋白酶和类木瓜蛋白酶作为新型冠状病毒SARS-CoV-2药物治疗的潜在靶点。
RSC Adv. 2023 Dec 6;13(50):35500-35524. doi: 10.1039/d3ra06479d. eCollection 2023 Nov 30.
6
Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.SARS-CoV 和 SARS-CoV-2 主要蛋白酶的结构与功能及其抑制作用：全面综述。
Eur J Med Chem. 2023 Nov 15;260:115772. doi: 10.1016/j.ejmech.2023.115772. Epub 2023 Aug 28.
7
M-targeted anti-SARS-CoV-2 inhibitor-based drugs.基于M靶点的抗SARS-CoV-2抑制剂的药物。
J Chem Res. 2023 Jul 3;47(4):17475198231184799. doi: 10.1177/17475198231184799. eCollection 2023 Jul-Aug.
8
Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors.大型文库对接新型 SARS-CoV-2 主蛋白酶非共价和共价抑制剂。
Protein Sci. 2023 Aug;32(8):e4712. doi: 10.1002/pro.4712.
9
Discovery of Chalcone-Based Hybrid Structures as High Affinity and Site-Specific Inhibitors against SARS-CoV-2: A Comprehensive Structural Analysis Based on Various Host-Based and Viral Targets.基于查尔酮的杂合结构作为高亲和力和特异性针对 SARS-CoV-2 的抑制剂的发现：基于各种宿主和病毒靶标的综合结构分析。
Int J Mol Sci. 2023 May 15;24(10):8789. doi: 10.3390/ijms24108789.
10
SARS-CoV-2 Nucleocapsid Protein Is a Potential Therapeutic Target for Anticoronavirus Drug Discovery.严重急性呼吸综合征冠状病毒 2 核衣壳蛋白是抗病毒药物研发的潜在治疗靶点。
Microbiol Spectr. 2023 Jun 15;11(3):e0118623. doi: 10.1128/spectrum.01186-23. Epub 2023 May 18.
Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.
从沙特阿拉伯一名患有肺炎的男子中分离出一种新型冠状病毒。
N Engl J Med. 2012 Nov 8;367(19):1814-20. doi: 10.1056/NEJMoa1211721. Epub 2012 Oct 17.
4
The role of aldehyde oxidase and xanthine oxidase in the biotransformation of a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5.醛氧化酶和黄嘌呤氧化酶在代谢型谷氨酸受体亚型 5 的新型负变构调节剂生物转化中的作用。
Drug Metab Dispos. 2012 Sep;40(9):1834-45. doi: 10.1124/dmd.112.046136. Epub 2012 Jun 18.
5
Human Coronaviruses HCoV-NL63 and HCoV-HKU1 in Hospitalized Children with Acute Respiratory Infections in Beijing, China.中国北京急性呼吸道感染住院儿童中的人冠状病毒HCoV-NL63和HCoV-HKU1
Adv Virol. 2011;2011:129134. doi: 10.1155/2011/129134. Epub 2011 Jul 21.
6
Structure-based design, synthesis, and evaluation of peptide-mimetic SARS 3CL protease inhibitors.基于结构的 SARS 3CL 蛋白酶抑制剂的肽模拟物的设计、合成与评价。
J Med Chem. 2011 Dec 8;54(23):7962-73. doi: 10.1021/jm200870n. Epub 2011 Nov 9.
7
Human coronavirus NL63: a clinically important virus?人冠状病毒 NL63：一种具有临床重要性的病毒？
Future Microbiol. 2011 Feb;6(2):153-9. doi: 10.2217/fmb.10.166.
8
Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy.抗严重急性呼吸综合征冠状病毒化学、生物学及化疗研究进展
Annu Rep Med Chem. 2007 Feb 1;41:183-196. doi: 10.1016/S0065-7743(06)41011-3.
9
Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors.一系列强效氯吡啶酯衍生的SARS-CoV 3CLpro抑制剂的设计、合成及抗病毒疗效
Bioorg Med Chem Lett. 2008 Oct 15;18(20):5684-8. doi: 10.1016/j.bmcl.2008.08.082. Epub 2008 Aug 28.
10
Aryl methylene ketones and fluorinated methylene ketones as reversible inhibitors for severe acute respiratory syndrome (SARS) 3C-like proteinase.芳基亚甲基酮和氟化亚甲基酮作为严重急性呼吸综合征（SARS）3C样蛋白酶的可逆抑制剂。
Bioorg Chem. 2008 Oct;36(5):229-40. doi: 10.1016/j.bioorg.2008.01.001. Epub 2008 Mar 4.