In this study, a series of new Schiff bases, based on a pyrimidine core, were synthesized in two steps. The structures of these newly synthesized Schiff bases were completely characterized. The presence of characteristic -N=CH proton peaks proving the formation of imine supports the structures of the compounds. The cytotoxic activity studies were done towards human cancer cell lines. The results show that the related molecules had antiproliferative activity on cancerous cells. To compare the chemical and biological activities of pyrimidine derivatives were performed using Gaussian software and Maestro Molecular modeling platform by Schrodinger, respectively. Afterwards, ADME/T analysis was performed to examine the possibility of pyrimidine derivatives being drugs.