title: Diphenylpyrroles: Novel p53 activators.
abstract: 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.
authors.affiliation: Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt. Electronic address: s.m.gomha@hotmail.com.
authors.forename: Sobhi M
authors.initials: SM
authors.lastname: Gomha
authors.affiliation: Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
authors.forename: Taha M A
authors.initials: TM
authors.lastname: Eldebss
authors.affiliation: Research Unit, Saco Pharm. Co., 6th October City, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Abdulla
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884 Egypt.
authors.forename: Abdelrahman S
authors.initials: AS
authors.lastname: Mayhoub
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011758:Pyrroles; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Benzimidazopyrimidine; Pyrazolopyrimidine; Pyrroles; Triazolopyrimidine; p53-specific ubiquitin E3 ligase HDM2