Design, synthesis and biological activity studies of new kinase inhibitors

Since cancer is a multifactorial disease, it has many reasons. Cancer was the second leading cause of death worldwide after cardiovascular disease, with an estimated 9.6 million deaths in 2018 alone, according to the World Health Organization report. Kinases constitute the largest gene family covering 1.7% of the human genome and constitute the second largest gene family for drug discovery. Small molecular kinase inhibitors are of great interest as novel anticancer therapeutics used in clinical evaluation. In this doctoral thesis, some new pyridine and pyrimidine ring-containing compounds were synthesized to develop new anticancer agents. Imatinib was used as the precursor compound and various modifications were made to increase the activity. The synthesis of the compounds were carried out according to literature methods. Structure determinations of the compounds were carried out using IR, 1H-NMR, 13C-NMR, 2D-NMR and APCI spectroscopic methods. Anticancer activity tests were performed in vitro against A549, C6, MCF-7, HepG2, HT29 and Panc-1 cell lines. Further activity studies were carried out for the compounds 5i, 5j, 7i and 7j. The inhibitory potential of the compounds against PDGFRα and ABL enzymes was investigated.