1542066-24-9

Upstream product

• 1051871-37-4 5-(3-(1H-imidazol-1-yl)propyl)-4-(4-bromophenyl)-3-phenyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one 
• 5036-48-6 3-(1H-imidazol-1-yl)propan-1-amine 
• 17583-35-6 2-(3-(1H-imidazol-1-yl)propyl)isoindoline-1,3-dione 
• 498568-17-5 4-benzoyl-5-(4-bromophenyl)-3-hydroxy-1-[3-(1H-imidazol-1-yl)propyl]-2,5-dihydro-1H-pyrrol-2-one 
• 41167-58-2 2-hydroxy-4-oxo-4-phenyl-but-2-enoic acid methyl ester 
• 98-86-2 acetophenone 

Relevant academic research and scientific papers

Gyrrolone and pyrromonazole compound and its use as medicine

The present invention belongs to the technical field of medicine. Provided in the present invention is pyrrolidone compounds, including optical isomers, racemates, cis and trans isomers and any combination thereof or pharmaceutically acceptable salts thereof, having a structure as shown in formula (I). The compounds of the present invention can be used as a small molecule inhibitor for p53-MDM2/X protein interactions. The compounds of the present invention can be used to prepare antineoplastic or anti-inflammatory drugs.

Double-edged swords as cancer therapeutics: Novel, orally active, small molecules simultaneously inhibit p53-MDM2 interaction and the NF-κB pathway

Simultaneous inactivation of p53 and hyperactivation of nuclear factor-κB (NF-κB) is a common occurrence in human cancer. Currently, antitumor agents are being designed to selectively activate p53 or inhibit NF-κB. However, there is no concerted effort yet to deliberately design inhibitors that can simultaneously do both. This paper provided a proof-of-concept study that p53-MDM2 interaction and NF-κB pathway can be simultaneously targeted by a small-molecule inhibitor. A series of pyrrolo[3,4-c]pyrazole derivatives were rationally designed and synthesized as the first-in-class inhibitors of p53-MDM2 interaction and NF-κB pathway. Most of the compounds were identified to possess nanomolar p53-MDM2 inhibitory activity. Compounds 5q and 5s suppressed NF-κB activation through inhibition of IκBα phosphorylation and elevation of the cytoplasmic levels of p65 and phosphorylated IKKα/β. Biochemical assay for the kinases also supported the fact that pyrrolo[3,4-c]pyrazole compounds directly targeted the NF-κB pathway. In addition, four compounds (5j, 5q, 5s, and 5u) effectively inhibited tumor growth in the A549 xenograft model. Further pharmacokinetic study revealed that compound 5q exhibited excellent oral bioavailability (72.9%).