The current dissertation describes a multidisciplinary research project centered on the discovery and investigation of the anticancer activities exhibited by novel piperazinylpyrimidine derivatives designed to target kinases protein family. Primary screening of the antiproliferative effects implemented by these successfully synthesized new agents has resulted in the candidacy of 4 , 15 , and 16 as not only prototype representatives of the class, but surprisingly also as optimized agents for either globally cytotoxic, 16 , or selectively cytostatic, 4 and 15 , agents. Subjecting 4 , 15 , and 16 to screening tests aiming at measuring their binding to or their functional inhibition of selected sets of kinases has revealed the tendency of 4 to target PDGFR subfamily and the ability of 4 , 15 , and 16 to recognize CSNK1D. Docking as well as binding profiles comparative studies hypothesize 4 , 15 , and 16 as type-I kinase inhibitors. Further preclinical investigation of 15 against MDA-MB-468 triple negative breast cancer cell line revealed that 15 exhibits a time as well as dose-dependent antiproliferative activity mediated by the induction of both time and dose independent G2/M arrest and dose dependent apoptosis. Globally studying the molecular events accompanied with the 15 /MDA-MB-468 incidence has revealed the phosphorylation of TP53 and the consequent activation of its transcriptional activity as a hallmark molecular event relevant to the above observed effects on the cellular, cell cycle, and programmed cell death levels. Apart from the above experimentally oriented investigation, another theoretically driven inquiry was pursued aiming at studying the inherent ability of certain kinases to be more promiscuous towards binding to small molecules than others. Throughout the analysis of a reported dataset, dephosphorylated members of PDGFR subfamily were found to more potently bind to structurally diverse kinase inhibitors compared to INSR subfamily. A molecular dynamics study was performed to compare between the topological, energetic, and dynamic properties of the binding area usually targeted by kinase inhibitors in both KIT, as a representative of the more promiscuous PDGFR subfamily, and INSR, as a representative of the less promiscuous INSR subfamily. Interestingly enough, the binding area in both kinases showed significantly different properties which, to a large extent, can explain their different overall attitudes towards binding small molecules. As a representative example, the binding area of INSR tends to be more energetically self-stabilizing than that in KIT. Additionally, the topological analysis revealed that the binding are in KIT tends to be more rigid and to have bigger size than that of INSR. The current work has successfully cross-implemented experimental, theoretical, and computational studies aiming at the development of novel kinase inhibitors and/or promising anticancer preclinical candidates.