发现4-（（喹啉-8-基硫代）甲基）苯甲酰胺衍生物作为一类新的SARS-CoV-2 nsp13抑制剂。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-03-25 DOI:10.1016/j.bmcl.2025.130207

Danchen Fan , Yuanting Huang , Rui Yao , Guo Zhang , Shengyong Yang , Linli Li

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引用次数: 0

摘要

抗病毒药物对COVID-19提供了重要的保护，然而，SARS-CoV-2变体和耐药突变体的出现要求开发具有替代作用机制的新型抗冠状病毒药物。SARS-CoV-2的非结构蛋白13 （nsp13）在冠状病毒的复制中起保守作用，已被确定为一个有希望的靶点。在这项研究中，我们报道了一系列4-（（喹啉-8-基硫）甲基）苯甲酰胺衍生物作为SARS-CoV-2 nsp13抑制剂。通过构效关系（SAR）分析，我们发现化合物6r对nsp13具有较强的抑制作用，IC50值为0.28 ± 0.11 μM。总之，我们发现了一种新的有效的SARS-CoV-2 nsp13抑制剂，可以作为进一步开发针对SARS-CoV-2 nsp13的药物的有希望的先导化合物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Discovery of 4-((quinolin-8-ylthio)methyl)benzamide derivatives as a new class of SARS-CoV-2 nsp13 inhibitors

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Discovery of 4-((quinolin-8-ylthio)methyl)benzamide derivatives as a new class of SARS-CoV-2 nsp13 inhibitors

Antivirals have provided important protection against COVID-19, however, the emergence of SARS-CoV-2 variants and drug-resistant mutants calls for the development of novel anti-coronavirus drugs with alternative mechanisms of action. The nonstructural protein 13 (nsp13) of SARS-CoV-2 plays a conserved role in the replication of coronaviruses and has been identified as a promising target. In this study, we report a series of 4-((quinolin-8-ylthio)methyl)benzamide derivatives as inhibitors of SARS-CoV-2 nsp13. Through structure-activity relationship (SAR) analyses, we identified compound 6r, which demonstrated potent inhibition of nsp13 with an IC₅₀ value of 0.28 ± 0.11 μM. Collectively, we discovered a new potent SARS-CoV-2 nsp13 inhibitor, which could be taken as a promising lead compound for further drug development targeting SARS-CoV-2 nsp13.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.