Journal
VIRUSES-BASEL
Volume 15, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/v15020544
Keywords
antivirals; prodrugs; carbocyclic nucleosides; viral polymerase; SARS-CoV-2; influenza virus; norovirus
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In recent decades, both 4'-modified nucleosides and carbocyclic nucleoside analogs have been studied extensively due to their potential anti-viral activity against HIV, HCV, RSV, and SARS-CoV-2. In this study, we designed compounds that combine both features and successfully synthesized a series of novel 4'-substituted carbocyclic uracil derivatives and their corresponding monophosphate prodrugs. These compounds were evaluated against a panel of RNA viruses including SARS-CoV-2, influenza A/B viruses, and norovirus.
Over the past decades, both 4 '-modified nucleoside and carbocyclic nucleoside analogs have been under the spotlight as several compounds from either family showed anti-HIV, HCV, RSV or SARS-CoV-2 activity. Herein, we designed compounds combining these two features and report the synthesis of a series of novel 4 '-substituted carbocyclic uracil derivatives along with their corresponding monophosphate prodrugs. These compounds were successfully prepared in 19 to 22 steps from the commercially available (-)-Vince lactam and were evaluated against a panel of RNA viruses including SARS-CoV-2, influenza A/B viruses and norovirus.
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