New nucleoside analogues and their 5′-triphosphates: Synthesis and biological properties

Bicyclic furano-and pyrrolo[2,3- d ]pyrimidine nucleosides and purine nucleosides modified at the N 1 atom and/or the 6-position have been synthesized. Among the tested nontoxic bicyclic nucleosides and N 6 -carboxyalkyladenosines, only furo[2,3- d ]pyrimidine with the C 10 H 21 substituent and N 6 -carboxymethyladenosine exhibit moderate anti-HCV activity in the virus replicon system and N 1 -hydroxyinosine exhibits high anti-HCV activity and significant cytotoxicity. The corresponding 5′-triphosphates have been synthesized and studied as substrates/inhibitors of HCV enzymes: NS5B protein (RNA-dependent RNA polymerase) and NS3 protein (NTP-dependent RNA helicase).