title: Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors.
abstract: 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.
authors.affiliation: National Organization for Drug Control & Research, PO Box 29, Cairo, Gizaa 112313, Egypt. dino1421@hotmail.com
authors.forename: Diaa A
authors.initials: DA
authors.lastname: Ibrahim
authors.forename: Amira M
authors.initials: AM
authors.lastname: El-Metwally
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D051357:Cyclin-Dependent Kinase 2