Synthesis and evaluation of N-arylindazole-3-carboxamide derivatives as novel antiviral agents against SARS-CoV-2

Bioorg Med Chem Lett. 2024 Dec 1:114:130015. doi: 10.1016/j.bmcl.2024.130015. Epub 2024 Nov 1.

Abstract

N-Arylindazole-3-carboxamide derivatives synthesized from an anti-MERS-CoV hit compound showed potent inhibitory activities against SARS-CoV-2. Among them, 5-chloro-N-(3,5-dichlorophenyl)-1H-indazole-3-carboxamide (4a) exhibited a potent inhibitory effect (EC50 = 0.69 µM), low cytotoxicity, and satisfactory in vitro PK profiles. Thus, N-arylindazole-3-carboxamide 4a provides a novel template for future development of anti-coronavirus agents.

Keywords: Antiviral; Coronavirus; MERS-CoV; N-Arylindazole-3-carboxamide; SARS-CoV-2.

MeSH terms

  • Animals
  • Antiviral Agents* / chemical synthesis
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • COVID-19 Drug Treatment
  • Humans
  • Indazoles* / chemical synthesis
  • Indazoles* / chemistry
  • Indazoles* / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • SARS-CoV-2* / drug effects
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Antiviral Agents
  • Indazoles