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.
COVID-19 , Influenza A virus , Prodrugs , Humans , Antiviral Agents/pharmacology , Hepatitis C Antibodies , Influenza B virus , Nucleosides , Prodrugs/pharmacology , SARS-CoV-2 , Uracil
Based on the anti-hepatitis C activity of 2'-C-methyl-adenosine and 2'-C-methyl-guanosine, a series of new modified purine 2'-C-methyl nucleosides was prepared as potential anti-hepatitis C virus agents. Herein, we report the synthesis of both 6-modified and 2-modified purine 2'-C-methyl-nucleosides along with their anti-HCV replication activity and cytotoxicity in different cells.
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Hepacivirus/drug effects , Purine Nucleosides/chemistry , Purine Nucleosides/pharmacology , Animals , Antiviral Agents/chemical synthesis , Cell Line , Cell Survival/drug effects , Hepatitis C/drug therapy , Humans , Purine Nucleosides/chemical synthesis
