The Hydrazine Moiety in the Synthesis of Modified Nucleosides and Nucleotides

Synthetic nucleoside mimics are re-emerging as crucial contenders for antiviral and anticancer medications. While, Ribavirin stands out for its unique antiviral properties, predominantly associated with its distinctive triazole heterocycle as a nucleobase, the exploration of alternative nitrogen-based aromatic heterocycles hold great promises for the discovery of novel bioactive nucleoside mimics. Although nucleoside derivatives synthesized from hydrazine-ribose units have been in development for many decades, they have been little evaluated biologically and even less for their antiviral properties. With the aim of taking a closer look at these under-explored derivatives and investigating their synthetic pathways, this review provides an overview of the molecular design, the chemical synthesis, and the biological activity, when available, of these nucleoside analogues. Overall, the entire body of work already done motivates further exploration of these analogues and encourages us of formulating structurally novel nucleoside drug candidates featuring innovative mode of action. Nucleoside derivatives synthesized from hydrazine-ribose units have been in development for a long time, but surprisingly no inventory has been carried out to date about their synthesis and biological properties. With the aim of filling this gap, this review provides an examination of the chemical synthesis, and potential biological activity of these under-explored derivatives. image