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J Org Chem
. 2025 Jul 21.
doi: 10.1021/acs.joc.5c00918. Online ahead of print. Synthesis and Inhibitory Assessment of ACE2 Inhibitors for SARS-CoV-2: An In Silico and In Vitro Study
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 , Franklin Aigbirhio 2 , Véronique Gouverneur 1
Affiliations
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.
. 2025 Jul 21.
doi: 10.1021/acs.joc.5c00918. Online ahead of print. Synthesis and Inhibitory Assessment of ACE2 Inhibitors for SARS-CoV-2: An In Silico and In Vitro Study
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 , Franklin Aigbirhio 2 , Véronique Gouverneur 1
Affiliations
- PMID: 40686086
- DOI: 10.1021/acs.joc.5c00918
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.