A Multi-Component Reaction to 6-Aminothiouracils: Synthesis, Mechanistic Study and Antitumor Activity

The present work deals with design, synthesis, mechanistic study and biological evaluation of novel, diverse compounds as potential inhibitors of cyclin-dependent kinase 2 (CDK2). Multi-complex-based method has been suggested to generate a comprehensive pharmacophore map of cyclin-dependent kinase 2 (CDK2) based on a collection of 13 crystal structures of human CDK2 inhibitor complex. The proposed chromeno [4',3':4,5] pyrido [2,3-d] pyrimidine-1,7-dione derivatives were prepared via a multicomponent reaction of 6-aminothiouracil with salicylic aldehyde and acetylacetic ester. The elucidation of the reaction mechanism was investigated and was confirmed by synthetic and spectroscopic methods. All the newly synthesized compounds were tested as CDK2, as antitumor agents and all of them were found to be active.