Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2

被引：23

作者：

Shin, Young Sup ^{[1
]}

Lee, Jun Young ^{[1
]}

Noh, Soojin ^{[1
]}

Kwak, Yoonna ^{[1
]}

Jeon, Sangeun ^{[2
]}

Kwon, Sunoh ^{[3
]}

Jin, Young-hee ^{[4
]}

Jang, Min Seong ^{[5
]}

Kim, Seungtaek ^{[2
]}

Song, Jong Hwan ^{[1
]}

Kim, Hyoung Rae ^{[1
]}

Park, Chul Min ^{[1
]}

机构：

[1] Korea Res Inst Chem Technol, Ctr Convergent Res Emerging Virus Infect CEVI, 141 Gajeong Ro, Daejeon 34114, South Korea

[2] Inst Pasteur Korea, Zoonot Virus Lab, Seongnam Si 13488, Gyeonggi Do, South Korea

[3] Korea Inst Oriental Med, Herbal Med Res Div, Daejeon 34054, South Korea

[4] Korea Inst Oriental Med, KM Applicat Ctr, Daegu 41062, South Korea

[5] Korea Inst Toxicol, Dept Nonclin Studies, Daejeon 34114, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2021年 / 31卷

基金：

新加坡国家研究基金会;

关键词：

SARS-CoV-2; Cyclic sulfonamide; Coronavirus; Inhibitor; Structure activity relationship;

D O I：

10.1016/j.bmcl.2020.127667

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide derivatives as novel SARS-CoV-2 inhibitors. Compound 13c of the synthesized compounds exhibited robust inhibitory activity (IC50 = 0.88 mu M) against SARS-CoV-2 without cytotoxicity (CC50 > 25 mu M), with a selectivity index (SI) of 30.7. In addition, compound 13c exhibited high oral bioavailability (77%) and metabolic stability with good safety profiles in hERG and cytotoxicity studies. The present study identified that cyclic sulfonamide derivatives are a promising new template for the development of anti-SARS-CoV-2 agents.

引用

页数：5

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