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. Epub 2020 Nov 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • COVID-19 Drug Treatment
  • Cell Line
  • Chlorocebus aethiops
  • Cricetulus
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Rats
  • SARS-CoV-2 / drug effects*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Antiviral Agents
  • Sulfonamides