Aiming to perform the structural optimization of CM-M345 (1) and BP-C4 (2) and SAR studies, 33 compounds were planned, synthesized, and evaluated for their antiproliferative activity in human colorectal cancer HCT116 cells expressing wt p53 and its p53-null isogenic derivative HCT116 p53−/− cells, as well as in human normal fibroblasts cells to assess their selectivity towards cancer cells. This evidence concerns the gene TP53 and colorectal cancer.