Synthesis and In Vitro Evaluation of Adenosine Deaminase Resistant N-6 Aminal and Thioaminal Prodrugs of Cordycepin

Cordycepin (3;-deoxyadenosine) is a potent anti-leukemic, anti-fungal, and anti-parasitic nucleoside antibiotic. Unfortunately, the biological activity of cordycepin is attenuated by its rapid conversion to 3;-deoxyinosine by adenosine deaminase (ADA). We have synthesized a series of ADA-resistant N-aminal and N-thioaminal cordycepin derivatives, which are protected from inactivation by deamination and yet retain biological activity. These compounds are hydrolyzed at various rates to efficiently release the parent drug cordycepin, and likely serve as simple hydrolytically activated prodrugs.