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

tetano

Editor, Senior Moderator
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[SUP] 1 [/SUP], Jieyu He[SUP] 2 [/SUP], Layla Hosseini-Gerami[SUP] 3 [/SUP], Morgan Thomas[SUP] 3 [/SUP], Stephen Thompson[SUP] 2 [/SUP], Joseph Ford[SUP] 1 [/SUP], Sebastiano Ortalli[SUP] 1 [/SUP], Zijun Chen[SUP] 1 [/SUP], Gianluca Destro[SUP] 1 [/SUP], Andreas Bender[SUP] 3 [/SUP], Franklin Aigbirhio[SUP] 2 [/SUP], Véronique Gouverneur[SUP] 1 [/SUP]



Affiliations
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 pIC[SUB]50[/SUB] assays confirming the inhibitory potency of the synthesized analogues. Lastly, this route was applied to the synthesis of novel [SUP]18[/SUP]F-labeled ACE2 inhibitors for PET imaging applications.


 
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