Nucleosides are ubiquitous in biological systems making them the focus of research devoted to finding new and potent therapeutic compounds. There are a number of modified nucleoside drugs on the market, however in recent years there have been increasing reports of resistance through “escape mutations” that alter the target enzymatic binding site or the pathway that the drugs are designed to interrupt. Recent studies have shown that flexible drug candidates can overcome this predicament by adapting to altered binding sites and engaging ‘secondary amino acids that are not usually required for recognition or involved in the mechanism of áàtion. It is for this. reason that the development of compounds that can change conformation while maintaining recognition by the target enzyme would be highly desirable, and has thus made flexible nucleoside analogues the focal point for the development of new potent therapeutics. With this goal in mind, we have designed a series of novel carbocyclic nucleoside analogues with a flexible purine/pyrimidine hybrid base scaffold. It is hoped these unique analogues will be capable of overcoming viral resistance mechanisms resulting from binding site mutations.