Design, Synthesis & Biological Evaluation of Novel Pyrimido[4,5-d]pyrimidine Derivatives as Tyrosine Kinase Inhibitors

Abstract

Pyrimidopyrimidines, a • condensed heterocycles have attracted considerable interest in the recent years. Its derivatives have been known to display a wide range of pharmacological activities, and their . potent inhibitory properties as regards the tyrosine kinase domain of epidermal growth factor receptor, 5-phosphoribosyl-1-pyrophosphate synthetase and dihydrofolate reductase have been fully demonstrated. Numerous reports delineate the antitumor, antiviral (as inhibitor of herpes simplex v1rus reactivation and viral protein synthesis), antioxidant (as lipid peroxidation inhibitors), antifungal and hepatoprotective activity of these compounds. In our program to develop CDK2 inhibitors as anti-cancer agents, we have designed, synthesized, and biologically evaluated trisubstituted pyrimido[4,5-d]pyrimidines as inhibitors of tumor cell proliferation at the National Cancer Institute (NCI), USA.