肽基 α-酮酰胺和 α-酮杂环对诺如病毒 3CL 蛋白酶的强效抑制作用。
Potent inhibition of norovirus 3CL protease by peptidyl α-ketoamides and α-ketoheterocycles.
机构信息
Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
出版信息
Bioorg Med Chem Lett. 2012 Jul 15;22(14):4820-6. doi: 10.1016/j.bmcl.2012.05.055. Epub 2012 May 26.
Abstract
A series of structurally-diverse α-ketoamides and α-ketoheterocycles was synthesized and subsequently investigated for inhibitory activity against norovirus 3CL protease in vitro, as well as anti-norovirus activity in a cell-based replicon system. The synthesized compounds were found to inhibit norovirus 3CL protease in vitro and to also exhibit potent anti-norovirus activity in a cell-based replicon system.
摘要
合成了一系列结构多样的α-酮酰胺和α-酮杂环化合物，并对其进行了体外抑制诺如病毒 3CL 蛋白酶活性以及基于细胞的复制子系统抗诺如病毒活性的研究。结果表明，所合成的化合物在体外能够抑制诺如病毒 3CL 蛋白酶，并且在基于细胞的复制子系统中具有很强的抗诺如病毒活性。
相似文献
1
Potent inhibition of norovirus 3CL protease by peptidyl α-ketoamides and α-ketoheterocycles.
Bioorg Med Chem Lett. 2012 Jul 15;22(14):4820-6. doi: 10.1016/j.bmcl.2012.05.055. Epub 2012 May 26.
2
Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors.
Bioorg Med Chem Lett. 2013 Jan 1;23(1):62-5. doi: 10.1016/j.bmcl.2012.11.026. Epub 2012 Nov 21.
3
Potent inhibition of norovirus by dipeptidyl α-hydroxyphosphonate transition state mimics.
Bioorg Med Chem Lett. 2013 Nov 1;23(21):5941-4. doi: 10.1016/j.bmcl.2013.08.073. Epub 2013 Aug 22.
4
Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease.
Eur J Med Chem. 2017 Feb 15;127:41-61. doi: 10.1016/j.ejmech.2016.12.033. Epub 2016 Dec 21.
5
Structure-based exploration and exploitation of the S subsite of norovirus 3CL protease in the design of potent and permeable inhibitors.
Eur J Med Chem. 2017 Jan 27;126:502-516. doi: 10.1016/j.ejmech.2016.11.027. Epub 2016 Nov 14.
6
Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease.
Eur J Med Chem. 2018 Jan 1;143:881-890. doi: 10.1016/j.ejmech.2017.12.014. Epub 2017 Dec 6.
7
Structure-guided design and optimization of dipeptidyl inhibitors of norovirus 3CL protease. Structure-activity relationships and biochemical, X-ray crystallographic, cell-based, and in vivo studies.
J Med Chem. 2015 Apr 9;58(7):3144-55. doi: 10.1021/jm5019934. Epub 2015 Mar 19.
8
Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors.
Bioorg Med Chem Lett. 2018 Jul 1;28(12):2165-2170. doi: 10.1016/j.bmcl.2018.05.012. Epub 2018 May 8.
9
Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease.
J Med Chem. 2016 Mar 10;59(5):1899-913. doi: 10.1021/acs.jmedchem.5b01464. Epub 2016 Feb 8.
10
Structure-Guided Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease.
J Med Chem. 2020 Oct 22;63(20):11945-11963. doi: 10.1021/acs.jmedchem.0c01252. Epub 2020 Oct 2.
引用本文的文献
1
Traditional Chinese medicine as a promising choice for future control of PEDV.
Virus Res. 2025 Jun;356:199572. doi: 10.1016/j.virusres.2025.199572. Epub 2025 Apr 10.
2
Potent small molecule inhibitors against the 3C protease of foot-and-mouth disease virus.
Microbiol Spectr. 2024 Apr 2;12(4):e0337223. doi: 10.1128/spectrum.03372-23. Epub 2024 Mar 11.
3
On the origins of SARS-CoV-2 main protease inhibitors.
RSC Med Chem. 2023 Oct 13;15(1):81-118. doi: 10.1039/d3md00493g. eCollection 2024 Jan 25.
4
Broad-spectrum coronavirus 3C-like protease peptidomimetic inhibitors effectively block SARS-CoV-2 replication in cells: Design, synthesis, biological evaluation, and X-ray structure determination.
Eur J Med Chem. 2023 May 5;253:115311. doi: 10.1016/j.ejmech.2023.115311. Epub 2023 Mar 31.
5
Heterogeneous Co-catalyzed direct 2-alkylation of azoles with ethers.
RSC Adv. 2018 Apr 12;8(25):13671-13674. doi: 10.1039/c8ra01796d. eCollection 2018 Apr 11.
6
Both Baicalein and Gallocatechin Gallate Effectively Inhibit SARS-CoV-2 Replication by Targeting M and Sepsis in Mice.
Inflammation. 2022 Jun;45(3):1076-1088. doi: 10.1007/s10753-021-01602-z. Epub 2021 Nov 25.
7
Norovirus Protease Structure and Antivirals Development.
Viruses. 2021 Oct 14;13(10):2069. doi: 10.3390/v13102069.
8
Synthetic and computational efforts towards the development of peptidomimetics and small-molecule SARS-CoV 3CLpro inhibitors.
Bioorg Med Chem. 2021 Sep 15;46:116301. doi: 10.1016/j.bmc.2021.116301. Epub 2021 Jul 3.
9
The Alpha Keto Amide Moiety as a Privileged Motif in Medicinal Chemistry: Current Insights and Emerging Opportunities.
J Med Chem. 2021 Apr 8;64(7):3508-3545. doi: 10.1021/acs.jmedchem.0c01808. Epub 2021 Mar 25.
10
The preclinical inhibitor GS441524 in combination with GC376 efficaciously inhibited the proliferation of SARS-CoV-2 in the mouse respiratory tract.
Emerg Microbes Infect. 2021 Dec;10(1):481-492. doi: 10.1080/22221751.2021.1899770.
本文引用的文献
1
Potent norovirus inhibitors based on the acyclic sulfamide scaffold.
Bioorg Med Chem. 2012 Mar 15;20(6):2111-8. doi: 10.1016/j.bmc.2012.01.030. Epub 2012 Feb 2.
2
Inhibition of noroviruses by piperazine derivatives.
Bioorg Med Chem Lett. 2012 Jan 1;22(1):377-9. doi: 10.1016/j.bmcl.2011.10.122. Epub 2011 Nov 15.
3
Cyclosulfamide-based derivatives as inhibitors of noroviruses.
Eur J Med Chem. 2012 Jan;47(1):59-64. doi: 10.1016/j.ejmech.2011.10.019. Epub 2011 Oct 20.
4
Potent inhibition of Norwalk virus by cyclic sulfamide derivatives.
Bioorg Med Chem. 2011 Oct 15;19(20):5975-83. doi: 10.1016/j.bmc.2011.08.054. Epub 2011 Aug 27.
5
Design and synthesis of inhibitors of noroviruses by scaffold hopping.
Bioorg Med Chem. 2011 Oct 1;19(19):5749-55. doi: 10.1016/j.bmc.2011.08.032. Epub 2011 Aug 22.
6
Design, synthesis, and evaluation of inhibitors of Norwalk virus 3C protease.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5315-9. doi: 10.1016/j.bmcl.2011.07.016. Epub 2011 Jul 14.
7
Reversible competitive α-ketoheterocycle inhibitors of fatty acid amide hydrolase containing additional conformational constraints in the acyl side chain: orally active, long-acting analgesics.
J Med Chem. 2011 Apr 28;54(8):2805-22. doi: 10.1021/jm101597x. Epub 2011 Mar 23.
8
Viral gastroenteritis in adults.
Recent Pat Antiinfect Drug Discov. 2011 Jan;6(1):54-63. doi: 10.2174/157489111794407877.
9
Biodegradable nanogels for oral delivery of interferon for norovirus infection.
Antiviral Res. 2011 Feb;89(2):165-73. doi: 10.1016/j.antiviral.2010.11.016. Epub 2010 Dec 7.
10
A structural study of norovirus 3C protease specificity: binding of a designed active site-directed peptide inhibitor.
Biochemistry. 2011 Jan 18;50(2):240-9. doi: 10.1021/bi1008497. Epub 2010 Dec 15.
Zotero 插件