Advances in the chemical and biological diversity of heterocyclic systems incorporating pyrimido[1,6-]pyrimidine and pyrimido[1,6-]pyrimidine scaffolds

Heterocycles incorporating a pyrimidopyrimidine scaffold have aroused great interest from researchers in the field of medical chemistry because of their privileged biological activities; they are used as anti-bacterial, antiviral, anti-tumor, anti-allergic, antihypertensive, anticancer, and hepatoprotective agents. Therefore, the present study aims to investigate the chemistry of heterocycles incorporating pyrimido[1,6- a ]pyrimidine and pyrimido[1,6- c ]pyrimidine skeletons and their biological characteristics. The main sections discuss (1) the synthetic routes to obtain substituted pyrimidopyrimidines, pyrimido[1,6- a ]pyrimidin-diones, pyrimidoquinazolines, tricyclic, tetracyclic, and binary systems; (2) the reactivity of the substituents attached to the pyrimidopyrimidine skeleton, including thione and amide groups, nucleophilic substitutions, condensations, ring transformations, and coordination chemistry; (3) compounds of this class of heterocycles containing a significant characteristic scaffold and possessing a wide range of biological characteristics. The current study provides an overview of the synthetic routes, reactivity and privileged biological characteristics of bicyclic heterocycles incorporating pyrimido[1,6- a ]pyrimidine and pyrimido[1,6- c ]pyrimidine cores.