Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors.

Novel derivatives of 2,4,5,6-tetrasubstituted pyrimidine cyclin-dependent kinase (CDK2) inhibitors was designed and synthesized. We built a library of proposed pyrimidine derivatives and by using pharmacophore and docking techniques we made our selections. We modified the proposed compounds due to the interaction of docked structures with the protein to achieve the best fit. The newly synthesized compounds showed potent and selective CDK2 inhibitory activities and inhibited in-vitro cellular proliferation in cultured human tumor cells. The design, synthesis and biological evaluation of these 2,4,5,6-tetrasubstituted pyrimidine derivatives are reported.