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.
Jun Young Lee  1 ,  Sangeun Jeon  2 ,  Jung-Eun Cho  3 ,  Sungmin Kim  3 ,  Hyoung Rae Kim  3 ,  Hyeung-Geun Park  4 ,  Seungtaek Kim  5 ,  Chul Min Park  6
Affiliations
  • 1. Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 24114, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 2. Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • 3. Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 24114, Republic of Korea.
  • 4. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: [email protected].
  • 5. Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, Republic of Korea. Electronic address: [email protected].
  • 6. Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 24114, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 24114, Republic of Korea. Electronic address: [email protected].
PMID: 39489229 DOI: 10.1016/j.bmcl.2024.130015
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.
Products