1448869-75-7

Upstream product

• 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 
• 95-79-4 5-chloro-2-methyl-benzenamine 
• 1620583-23-4 ethyl 2-bromo-5-((4-chloro-2-methylphenyl)(methylsulfonyloxy)methyl)-1-isopropyl-1H-imidazole-4-carboxylate 
• 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 
• 40137-29-9 2-methyl-4-chlorobenzaldehyde 

Downstream Products

• 1448866-33-8 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-(5-fluoro-2-methoxy-phenyl)-1-isopropyl-4-oxo-5,6,-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-66-7 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-(2,6-dimethoxy-pyridin-3-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-67-8 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-2-(4-methoxy-pyrimidin-5-yl)-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-72-5 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-(2-dimethylamino-4-methoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-83-8 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-2-(4-methoxy-2-methylamino-pyrimidin-5-yl)-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-84-9 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-(2-ethyl-6-methoxy-pyridin-3-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-85-0 2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-88-3 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-{2-[(2-hydroxy-ethyl)-methyl-amino]-4-methoxy-pyrimidin-5-yl}-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-89-4 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-[2-(2-hydroxy-ethyl amino)-4-methoxy-pyrimidin-5-yl]-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-98-5 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-[2-(3-hydroxy-3-methyl-azetidin-1-yl)-4-methoxy-pyrimidin-5-yl]-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448867-00-2 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-2-[2-(3-hydroxy-azetidin-1-yl)-4-methoxy-pyrimidin-5-yl]-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 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 
• 1620582-88-8 6-(4-chloro-2-methylphenyl)-1-(5-chloro-2-methylphenyl)-7-isopropyl-8-(4-methoxypyridin-3-yl)-6,7-dihydro-1H-purin-2(3H)-one 
• 1620583-22-3 8-bromo-6-(4-chloro-2-methylphenyl)-1-(5-chloro-2-methylphenyl)-7-isopropyl-6,7-dihydro-1H-purin-2(3H)-one 

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.

SUBSTITUTED PURINONE 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.

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.