1448869-67-7

Upstream product

• 87951-12-0 3-Dimethylamino-2-isocyanacrylsaeure-ethylester 
• 2999-46-4 Ethyl isocyanoacetate 
• 1260793-84-7 1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 72130-97-3 ((Z)-2-N,N-dimethylamino-1-ethoxycarbonyl-vinyl)-methylidyne-ammonium 

Downstream Products

• 1448869-68-8 2-bromo-5-[(4-chlorophenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 1448870-05-0 2-bromo-5-[(5-chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-ylamino)-(4-cyano-phenyl)-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid 
• 1448870-06-1 2-bromo-5-[(5-chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-ylamino)-(4-cyano-phenyl)-methyl]-1-isopropyl-1 H-imidazole-4-carboxylic acid ethyl ester 
• 1448870-08-3 2-bromo-5-[(3-chloro-2-fluoro-phenylamino)-(4-cyano-phenyl)-methyl]-1-isopropyl-1 H-imidazole-4-carboxylic acid 
• 1448870-09-4 2-bromo-5-[(3-chloro-2-fluoro-phenylamino)-(4-cyano-phenyl)-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 1448870-11-8 2-bromo-5-[(3-chloro-4-fluoro-phenylamino)-(4-cyano-phenyl)-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid 
• 1448870-12-9 2-bromo-5-[(3-chloro-4-fluoro-phenylamino)-(4-cyano-phenyl)-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester 
• 1448866-68-9 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-2-(4-methoxy-2-methylamino-pyrimidin-5-yl)-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-70-3 C₂₉H₂₈Cl₂N₄O₂ 
• 1448866-71-4 3-[5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-d]imidazol-2-yl]-4-ethyl-benzonitrile 
• 1448866-73-6 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-2-(2-dimethylamino-4-methoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-74-7 2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-75-8 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-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 
• 1448866-76-9 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-2-[2-(2-hydroxy-ethylamino)-4-methoxy-pyrimidin-5-yl]-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 

Relevant academic research and scientific papers

IMIDAXOPYROLONE COMPOUND AND APPLICATION THEREOF

Disclosed is a novel class of MDM2-p53 inhibitor compounds having an imidaxopyrolone structure, and specifically disclosed are compounds represented by formulas (I-1) and (I-2) and pharmaceutically acceptable salts thereof. (I-1), (I-2)

MDM2 Inhibitors

A compound capable of being used as a tumor inhibitor, a preparation method therefor, and application thereof. The compound has a structure represented by general formula I; a stereoisomer, an enantiomer, a raceme, a cis/trans isomer, a tautomer, and an isotopic variant of the compound are comprised; the compound can be used separately or in combination with other drugs for treating tumors or inflammatory diseases, or for treating other disorders or diseases mediated by the activity of MDM2 and/or MDM4, and shows prominent curative activity.

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 DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE

The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

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.