Bromodomain-containing protein 4 (BRD4) plays the extremely important physiological role in cancer, and the BRD4 inhibitors can effectively inhibit the proliferation of tumor cells. By taking BI-2536 (PLK1 and BRD4 inhibitor) as the lead compound, sixteen novel BRD4 inhibitors with the 4,4-difluoro-1-methyl-N,6-diphenyl-5,6-dihydro-4H-pyrimido[4,5-b] [1,2,4] triazolo[4,3-d] [1,4] diazepin-8-amine structure were designed and synthetized. Among the target compounds, compound 15 h exhibited outstanding inhibition for BRD4-BD1 (IC50 value of 0.42 μM) in the BRD4-BD1 inhibitory activity assay. Additionally, cell growth inhibition assay demonstrated that compound 15 h potently suppressed the proliferation of MV4-11 cells (IC50 value of 0.51 μM). Besides, compound 15 h induced apoptosis and G0/G1 cycle-arrest in MV4-11 leukemia cells effectively, and down-regulated the expression of c-Myc in a dose-dependent manner. In summary, the optimal compound 15 h is expected to become the clinical therapeutic drug for further research.