Design, Synthesis And In Vitro Biological Activity Of4-(4-substituted-piperazin-1-yl)Pyrimidin-2-amine Derivatives

The Wnt/β-catenin signaling pathway is a highly conserved pathway. It is not only involved in embryonic development, but also closely related to the occurrence of tumors. Aberrant activation of the Wnt/β-catenin signaling pathway is closely related to tumorigenesi. Therefore, it becomes a research focus to inhibit oncogenic β-catenin.In order to find β-catenin small-molecule inhibitors with high efficiency and selectivity,4,6-disubstituted pyrimidin were used as the precursors, and4,6-positions of pyrimidin ring were modified by the different groups. Eleven4-substituted piperazinylpyrimidin-2-amine derivatives were designed and synthesized. The compounds were further determined by IR,1H NMR,13C NMR, MS and HRMS; the biological activities of synthesized compounds in vitro were tested. The antitumor activities of all compounds in vitro were evaluated against human lung carcinoma cells (A549), uterine cervical cancer cell (HeLa), human colon cancer cells (SW480) and human ileocecal adenocarcinoma cells (HCT-8) by MTT assays. The results showed that11c can effectively inhibit the proliferation of SW480and HCT-8, the antitumor activities of4and12c were more effective than that of control drug5-fluorouracil (5-FU). Therefore, the two compounds possess potential to be developed into a broad-spectrum anticancer drug candidates. And then, the Wnt pathway activities of the compounds were made the preliminary evaluation. The results are discussed and could support the further design and screening of the (3-catenin/Tcf inhibitor.