Pyrimidine and fused pyrimidine derivatives as promising protein kinase inhibitors for cancer treatment

Pyrimidine ring and its fused derivatives including pyrazolo[3,4- d ]pyrimidine, pyrido[2,3- d ]pyrimidine, quinazoline, and furo[2,3- d ]pyrimidine compounds had received much interest due to their diverse biological potential, in addition fused pyrimidine are considered as bioisosteres with purines and consequently many pyrimidine and fused pyrimidine derivatives as pyrazolo[3,4- d ]pyrimidine, pyrido[2,3- d ]pyrimidine, quinazoline, and furo[2,3- d ]pyrimidine possessed promising anticancer activity. These pyrimidine derivatives exerted their anticancer potential through different action mechanisms; one of these mechanisms is inhibiting protein kinases that are considered as essential enzymes for controlling cell growth, differentiation, migration, and metabolism. The present review sheds the light on the anticancer significance of some privileged pyrimidine and fused pyrimidine derivatives via selective inhibition of protein kinases, revealing structure-activity relationships and some synthetic pathways used for constructing these scaffolds in an attempt to assist medicinal chemists to construct novel pyrimidines with higher selectivity as anticancer agents.