Design, synthesis, and biological evaluation of thioamide-linked spiropyrrolidine derivatives as novel 3CLpro inhibitors against SARS-CoV-2
文献类型：期刊论文
| 作者 | Guma, Samuel Desta5,6; Song, Kang4; Sun, Haiguo6; Yang, Lei5,6; Zhou, Zhaoyin3,4; Suo, Jin6 ; Bonku, Emmanuel Mintah5,6; Zheng, Wei2; Tian, Guanghui2; Jiang, Xiangrui1,5,6
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025-10-01 |
| 卷号 | 128页码:11 |
| 关键词 | SARS-CoV-2 3CL(pro) inhibitors Thioamide derivatives Spiropyrrolidine derivatives Nirmatrelvir HCoV-OC43 Antiviral Metabolic stability |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2025.118239 |
| 英文摘要 | A series of thioamide-linked spiropyrrolidine derivatives were synthesized and evaluated against SARS-CoV-2 3CL(pro). Among these compounds, 9g demonstrated remarkable inhibition of 3CL(pro) (IC50 = 35 nM), surpassing the inhibitory potency of the approved antiviral drug nirmatrelvir (IC50 = 54 nM). In cellular assays against HCoV-OC43 in Huh7 cells, 9g exhibited significant antiviral efficacy (EC50 = 0.52 mu M) and low cytotoxicity (CC50 > 10 mu M). Furthermore, 9g exhibited pharmacokinetic profiles comparable to that of nirmatrelvir, making it a promising candidate for further development. |
| 资助项目 | Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM0120231003] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[CASIMM0120234003] ; National Natural Science Foundation of China[U22A20379] ; Alliance of International Science Organizations (ANSO) through the ANSO Scholarship |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001499763300001 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318162]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Qiumeng; Zhang, Yan |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China 2.Vigonvita Life Sci Co Ltd, 108 Yuxin Rd, Suzhou 215123, Jiangsu, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guma, Samuel Desta,Song, Kang,Sun, Haiguo,et al. Design, synthesis, and biological evaluation of thioamide-linked spiropyrrolidine derivatives as novel 3CLpro inhibitors against SARS-CoV-2[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2025,128:11. |
| APA | Guma, Samuel Desta.,Song, Kang.,Sun, Haiguo.,Yang, Lei.,Zhou, Zhaoyin.,...&Shen, Jingshan.(2025).Design, synthesis, and biological evaluation of thioamide-linked spiropyrrolidine derivatives as novel 3CLpro inhibitors against SARS-CoV-2.BIOORGANIC & MEDICINAL CHEMISTRY,128,11. |
| MLA | Guma, Samuel Desta,et al."Design, synthesis, and biological evaluation of thioamide-linked spiropyrrolidine derivatives as novel 3CLpro inhibitors against SARS-CoV-2".BIOORGANIC & MEDICINAL CHEMISTRY 128(2025):11. |
入库方式： OAI收割
来源：上海药物研究所
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