2. Academic Validation
  3. Synthesis and Inhibitory Assessment of ACE2 Inhibitors for SARS-CoV-2: An In Silico and In Vitro Study

Synthesis and Inhibitory Assessment of ACE2 Inhibitors for SARS-CoV-2: An In Silico and In Vitro Study

  • J Org Chem. 2025 Aug 1;90(30):10941-10947. doi: 10.1021/acs.joc.5c00918.
Xiaoyun Wang 1,  Jieyu He 2,  Layla Hosseini-Gerami 3,  Morgan Thomas 3,  Stephen Thompson 2,  Joseph Ford 1,  Sebastiano Ortalli 1,  Zijun Chen 1,  Gianluca Destro 1,  Andreas Bender 3 4 5,  Franklin Aigbirhio 2,  Véronique Gouverneur 1
Affiliations

Affiliations

  • 1 Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
  • 2 Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, U.K.
  • 3 Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
  • 4 College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi 127788, UAE.
  • 5 STAR-UBB Institute, Babeş-Bolyai University, , Cluj-Napoca 400084, Romania.
PMID: 40686086 DOI: 10.1021/acs.joc.5c00918
Abstract

The angiotensin-converting enzyme 2 (ACE2) is pivotal as the cellular receptor for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus responsible for COVID-19. This study presents a novel synthetic route for four analogues of MLN-4760, a known inhibitor of ACE2, guided by in silico docking predictions. These synthetic advances enabled in vitro pIC50 assays confirming the inhibitory potency of the synthesized analogues. Lastly, this route was applied to the synthesis of novel 18F-labeled ACE2 inhibitors for PET imaging applications.

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