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

  • Bioorg Med Chem Lett. 2021 Jan 1:31:127667. doi: 10.1016/j.bmcl.2020.127667.
Young Sup Shin  1 ,  Jun Young Lee  1 ,  Soojin Noh  1 ,  Yoonna Kwak  1 ,  Sangeun Jeon  2 ,  Sunoh Kwon  3 ,  Young-Hee Jin  4 ,  Min Seong Jang  5 ,  Seungtaek Kim  2 ,  Jong Hwan Song  1 ,  Hyoung Rae Kim  1 ,  Chul Min Park  1
Affiliations
  • 1. Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea.
  • 2. Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea.
  • 3. Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea.
  • 4. KM Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu 41062, South Korea.
  • 5. Department of Non-Clinical Studies, Korea Institute of Toxicology, Yuseong-gu, Daejeon 34114, South Korea.
PMID: 33160024 DOI: 10.1016/j.bmcl.2020.127667
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.

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