Diphenylpyrroles: Novel p53 activators

•Blocking p53 binding site on HDM2 was believed to generate efficient antitumor agents.•Diphenylpyrroles were introduced and evaluated as a novel scaffold in the field of p53 activators.•New 4,5-diphenyl-3-heteroaryl-pyrroles were synthesized via reactions of enaminones with C- and N-nucleophiles.•Diphenylpyrroles scaffold has the advantage of synthetic protocol accessibility.

Cellular tumor antigen p53 is crucial for cancer prevention via different mechanisms. E3 ubiquitin-protein ligase HDM2 binds to p53, blocks its ability to activate transcription, and therefore acts as a negative regulator. Blocking p53 binding site on HDM2 was believed to generate efficient antitumor agents. So far, limited scaffolds were reported with HDM2 antagonist activity. Herein, diphenylpyrroles were introduced and evaluated as a novel scaffold in the field of p53 activators. An efficient synthesis of novel 3-heteroaryl-pyrroles is described via reactions of E-3-(dimethylamino)-1-(2-methyl-4,5-diphenyl-1H-pyrrol-3-yl)prop-2-en-1-one or E-1-(2-methyl-4,5-diphenyl-1H-pyrrol-3-yl)-3-morpholinoprop-2-en-1-one with hydrazine hydrate, phenyl hydrazine, hydroxylamine, various heterocyclic amines and active methylene compounds.

Graphical abstractAn efficient synthesis of novel 4,5-diphenyl-3-heteroaryl-pyrroles were synthesized and evaluated as a novel scaffold in the field of p53 activators.Figure optionsDownload full-size imageDownload as PowerPoint slide