Recent advances in nitrogen-containing heterocyclic compounds as receptor tyrosine kinase inhibitors for the treatment of cancer: Biological activity and structural activity relationship.

Erratic cell proliferation is the initial symptom of cancer, which can eventually metastasize to other organs. Before cancer becomes metastatic, its spread is triggered by pro-angiogenic factors including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), Platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and Platelet Factor (PF4), all of which are part of receptor tyrosine kinase (RTK) family. Receptor tyrosine kinases (RTKs) are cell-surface proteins and aresignaling enzymes that transfer ATP-phosphate to tyrosine residue substrates. Important biological processes like proliferation, differentiation, motility, and cell-cycle regulation are all possessedby these proteins. Unusual RTK expression is typically associated with cell growth abnormalities, which is linked to tumor acquisition, angiogenesis, and cancer progression. In addition to the already available medications, numerous other heterocyclic are being studied for their potential action against a variety of cancers. In the fight against cancer, in particular, these heterocycles have been used for their dynamic core scaffold and their inherent adaptability. In this review article, we have compiled last five years research work including nitrogen containing heterocycles that have targeted RTK. Herein, the SAR and activity of various compounds containing diverse heterocyclic (pyrimidine, indole, pyridine, pyrazole, benzimidazole, and pyrrole) scaffolds are discussed, and they may prove useful in the future for designing new leads against RTKs. Our focus in this manuscript is to comprehensively review the latest research on the biological activity and structural activity relationship of nitrogen compounds as RTK inhibitors. We believe that this may be an important contribution to the field, as it can help guide future research efforts and facilitate the development of more effective cancer therapies.