Transition state analogs contain an arrangement of substituents and a molecular geometry similar to that of the transition state of the substrate of a particular enzymatic reaction. For enzyme-catalyzed reactions, such analogs have proven to be potent, specific inhibitors of the associated enzyme. The use of transition state analogs as cancer chemotherapic agents has not been investigated. This application proposes the synthesis of two series of heterocycles that can potentially act as transition state analogs of purine nucleotide interconversion. The heterocyclic systems proposed are imidazothiadiazines in which an endocyclic sulfur atom has replaced either the 6-carbonyl carbon of hypoxanthine or the 2-carbonyl carbon of xanthine. The compounds were selected because tetravalent sulfur possesses a tetrahedral arrangement of substituents. Thus, the proposed compounds are designed to have an orientation of substituents similar to that which should exist at the carbonyl group during the transition state of the amination reaction normally occurring at that position of the parent purine. The specific compounds are proposed as transition state analogs of two critical enzymes in purine biosynthesis, adenylosuccinate synthetase and guanylate synthetase. New compounds that act as potent inhibitors of specific enzymes in purine metabolism are promising cancer chemotherapeutic agents. A successful application of the principle of transition state analogs would have broad implication for rational design of new drugs with predictable specificities.