The preparation of a series of 2,6,9-trisubstituted purines and the structure-activity data for the inhibition of cyclin dependent kinase, CDK2 are presented. Recent advances in molecular and cellular biology have greatly contributed to our understanding of the mechanisms of cell proliferation and of specific steps of the cell cycle as cells progress through mitosis. These studies have demonstrated that the cell cycle is tightly regulated by time dependent activation a family of serine/threonine kinases. These kinases are multiprotein complexes consisting of (a) a phosphorylated kinase called cyclin dependent kinase (CDK) and (b) a regulatory protein called cyclin. Different cyclin-CDK combinations control cell cycle steps such as growth, DNA replication, and cell division. One key member of the CDK family of enzymes is CDK2. CDK2/cyclin A activity has been shown to be essential for mammalian cell cycle progression at the G1/S boundary. Olomoucine is a specific inhibitor of CDK2 with an IC50 of approximately 7 gM, and in vivo studies using mammalian cells in culture demonstrate that olomoucine inhibits cell proliferation at an approximate concentration of 50 gg/mL. We report here the results of program to identify potent inhibitors of CDK2 to evaluate as potential therapeutic agents for controlling aberrant cell proliferation in a variety of diseases.