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The unprecedented novel coronavirus disease 2019 (COVID‐19) pandemic is a threat to global health and the economy. Since the outbreak of COVID‐19, great effort has been made to reposition existing drugs to shorten development timelines, in addition to vaccine development and drug discovery campaigns. Umifenovir is a broad‐spectrum antiviral agent used to treat influenza in China and Russia and is currently undergoing clinical trials for the treatment of COVID‐19. In this article, the synthesis of umifenovir analogues and their biological evaluation are reported. The inhibitory activities of analogues against the binding of the spike glycoprotein (S‐protein) of the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) to the ACE2 receptor, which is a possible mode of action for umifenovir to inhibit viral infection, were investigated.

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