Synthesis and investigation of antiviral activity of 3′-O-(aminoalkyl)-thymidines and their quaternary ammonium salts

Alkylation of 5'-O-tritylthymidine with dialkylaminoalkyl chlorides in the presence of sodium hydride yields 3'-O-dialkylaminoalkyl-5'-O-tritylthymidine derivatives 2 which were treated with an excess of iodomethane to afford the corresponding quaternary ammonium derivatives 3. Deprotected nucleosides 4 and 6 were obtained by refluxing 3 and 2, respectively, in 80% acetic acid. When the compounds 2-4 and 6 were investigated for activity against HSV and HIV, the trityl derivatives 2a and 2c were found active against HSV.