Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2. (1st January 2021)

• Record Type: Journal Article
• Authors: Shin, Young Sup; Lee, Jun Young; Noh, Soojin; Kwak, Yoonna; Jeon, Sangeun; Kwon, Sunoh; Jin, Young-hee; Jang, Min Seong; Kim, Seungtaek; Song, Jong Hwan; Kim, Hyoung Rae; Park, Chul Min
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 31(2021)
• Publication Date: 2021-01-01
• Subjects: SARS-CoV-2 -- Cyclic sulfonamide -- Coronavirus -- Inhibitor -- Structure activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127667
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 (IC50 = 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.