Synthesis and Mechanism of p53-MDM2 Inhibitors with Heterocyclic Structures: A Focused Review

P53 gene mutation is one of the important causes in tumors. p53-MDM2 (murine double minute 2) inhibitors can interrupt p53-dependent gene transcription activity, and inhibit p53-mediated apoptosis, block p53-MDM2/MDMx interaction, and significantly reduce DNA formation. In this article, we focused on the synthesis methods about nutlins and other p53 small molecule inhibitors, in order to find potential new structure for novel p53 small molecule inhibitor synthesizing. Mutation of the p53 gene is among the most important causes of tumors. Inhibitors of p53-MDM2 can impede p53-dependent gene transcription, inhibit p53-mediated apoptosis, block p53-MDM2/MDMx interaction, and significantly reduce DNA formation. In this review we discuss the synthesis of nutlins and other small-molecule p53 inhibitors, with an aim to inspire new structures and methods for the synthesis of future small-molecule p53 inhibitors.+image