1. Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2.
- Author
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Shin YS, Lee JY, Noh S, Kwak Y, Jeon S, Kwon S, Jin YH, Jang MS, Kim S, Song JH, Kim HR, and Park CM
- Subjects
- Animals, Antiviral Agents chemical synthesis, Antiviral Agents chemistry, Cell Line, Chlorocebus aethiops, Cricetulus, Dogs, Dose-Response Relationship, Drug, Humans, Mice, Microbial Sensitivity Tests, Molecular Structure, Rats, Structure-Activity Relationship, Sulfonamides chemical synthesis, Sulfonamides chemistry, COVID-19 Drug Treatment, Antiviral Agents pharmacology, Drug Discovery, SARS-CoV-2 drug effects, Sulfonamides pharmacology
- Abstract
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 (IC
50 = 0.88 μM) against SARS-CoV-2 without cytotoxicity (CC50 > 25 μM), 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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2021
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