1448866-35-0

Upstream product

• 1260793-84-7 1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 1448869-67-7 2-bromo-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 1448869-69-9 2-bromo-5-[(4-chloro-2-methyl-phenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 1448869-76-8 2-bromo-5-[(4-chloro-2-methyl-phenyl)-5-chloro-2-methyl-phenylamino]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 1448869-75-7 2-bromo-5-((4-chloro-2-methylphenyl)(5-chloro-2-methylphenylamino)methyl)-1-isopropyl-1H-imidazole-4-carboxylic acid 
• 1448869-74-6 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazole-4-one 
• 78495-63-3 (2-fluoro-6-methoxyphenyl)boronic acid 
• 1620583-23-4 ethyl 2-bromo-5-((4-chloro-2-methylphenyl)(methylsulfonyloxy)methyl)-1-isopropyl-1H-imidazole-4-carboxylate 

Relevant academic research and scientific papers

In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor

Small molecule inhibitors of the p53-MDM2 protein complex are under intense investigation in clinical trials as anti-cancer agents, including our first generation inhibitor NVP-CGM097. We recently described the rational design of a novel pyrazolopyrrolidinone core as a new lead structure and now we report on the synthesis and optimization of this to provide a highly potent lead compound. This new compound displayed excellent oral efficacy in our preclinical mechanistic in vivo model and marked a significant milestone towards the identification of our second generation clinical candidate NVP-HDM201.

IMIDAZOPYRROLIDINONE COMPOUNDS

The invention relates to compounds of formula (I): (I) as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.