Some of the synthesized analogs revealed promising antiproliferation properties against SJSA-1 (osteosarcoma), LNCaP (prostate), and MCF-7 (breast) cancer cell lines with the ability to dually inhibit MDM2-P53 and MDM4-p53 protein–protein interactions (IC50 = 26.1, 219.0; 35.9, 57.4 nM for MDM2-p53, MDM4-p53 corresponding to compounds 67 with R = 6-Cl, R’ = 3-OH, R′′ = 4-ClC6H4, R′′′ = 3-(3-phenyl-1H-pyrazol-1-yl)phenyl and R = 6-Cl, R′ = 3-OH, R′′ = 4-ClC6H4, R′′′ = 3-(1H-pyrazol-1-yl)phenyl, respectively) [35]. The gene discussed is TP53; the disease is osteosarcoma.