Synthesis of 4′-Substituted Carbocyclic Uracil Derivatives and Their Monophosphate Prodrugs as Potential Antiviral Agents

Abstract

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.

Keywords

• antivirals
• prodrugs
• carbocyclic nucleosides
• viral polymerase
• SARS-CoV-2
• influenza virus