Synthesis and Biological Evaluation of Pyrido(2,3-d)pyrimidines

There are four types of pyridopyrimidines namely pyrido[2,3-d], pyrido[3,4-d], pyrido[4,3-d]pyrimidines, and pyrido[3,2-d]pyrimidines. Different methods of preparation of pyrido[2,3-d]pyrimidines are summarized. Synthesis of pyrido[2,3-d]pyrimidines can be from pyrimidines derivatives or pyridine derivatives. We can start from pyrimidine derivatives and build a pyridine ring. 5,7-Diphenylpyrido[2,3-d]pyrimidines 3 and 4 were obtained by the reaction of 6-aminouracil (1) with alpha,beta-unsaturated ketone. 6-Amino-1,3-dimethyluracil 10 was reacted with an equimolar amount of Mannich bases 11a-c under an atmosphere of nitrogen to give pyridopyrimidines 14a-c via the formation of the intermediates 12a-c& 13a-c. 4-Benzylamino derivative 19 could be converted to pyrido[2,3-d]pyrimidine derivative 20 by the reaction with dimethylformamide/ dimethylacetal. In the same way, we can start from pyridine derivatives and build a pyrimidine ring. Different reported biological activities of pyrido[2,3-d]pyrimidines are discussed e.g. selective adenosine kinase inhibitors, analgesic, anti-inflammatory, antimicrobial and herbicides, selective inhibitor of the tyrosine kinase activities of the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) receptors.