6-Amino-4-methyl-8-( b -D-ribofiuunosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c]-pyridazine (Triciribine, TCN) has activity against human immunodeficiency virus (HIV) (IC50 = 40 nM). This prompted us to investigate the structural requirements and mode of action of TCN. The aims of this project were to improve the syntheses of key intermediates and to elaborate the structure-activity requirements of TCN as an inhibitor of HIV. It was established that 2-amino-5-bromo-3,4-dicyanopyrrole, 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine, toyocamycin and triciribine were the key intermediates in the syntheses of the desired triciribine analogs. Therefore, we designed and developed efficient and high yielding syntheses for the latter three intermediates. To better our understanding of the mechanism of action of TCN, we pursued several structure-activity relationship studies. In a series of investigations designed to specifically explore the structural requirements for the sugar moiety at the N-8 position of TCN for biological activity, our first investigation explored the requirements for rigidity of the ribosyl moiety. That study established that a disruption of the rigidity of ribosyl moiety adversely affected phosphorylation and therefore biological activity. Our second study explored the hydroxyl requirements of the ribosyl moiety at the N-8 position of TCN and established that dehydroxylation of the ribosyl moiety adversely affected phosphorylation and biological activity. Our third study explored the orientation requirements of the hydroxyl groups of the ribosyl moiety at the N-8 position of TCN by replacing it with a b -D-arabinofuranose or a b -D-xylofuranose sugar. No cellular pathology was observed in HIV infected cells treated with the b -D-xylofuranose sugar analog suggesting that this analog protected the cells from the destructive effect of HIV. To explore the effect of substitutions on the tricyclic ring system of TCN for biological activity, our fourth study explored substitutions at the 2-position of TCN. It appears that a substitution at the 2-position of TCN leads to a loss in antiviral activity. Finally, our fifth study explored the effects on phosphorylation and antiviral activity when the 6-amino group of TCN was acylated. This study established that a heptanoyl group on the 6-amino group of TCN has the optimum carbon chain length for activity against HIV-1. Interestingly, this compound has the same activity as that of TCN, suggesting a prodrug effect. Through this work, we better understand TCN as an antiviral agent and have a foundation and direction for future studies on TCN.