1429385-27-2

Upstream product

• 29559-24-8 4-chlorophenylnitromethane 
• 622-95-7 4-chlorobenzyl bromide 
• 1429385-26-1 (5R,6R)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-4-((S)-1-((3,4-dimethoxybenzyl)oxy)butan-2-yl)morpholin-3-one 
• 1429385-25-0 2-chloro-N-((1R,2R)-2-(3-chlorophenyl)-1-(4-chlorophenyl)-2-hydroxyethyl)acetamide 
• 1429385-24-9 (5R,6R)-6-(3-chlorophenyl)-5-(4-chlorophenyl)morpholin-3-one 
• 1429382-53-5 (1R,2R)-2-amino-1-(3-chlorophenyl)-2-(4-chlorophenyl)ethanol 

Downstream Products

• 1429385-22-7 2-((2R,5R,6R)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-4-((S)-1-(ethylsulfonyl)butan-2-yl)-3-oxomorpholin-2-yl)acetic acid 
• 1429385-23-8 2-((2S,5R,6R)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-4-((S)-1-(ethylsulfonyl)butan-2-yl)-3-oxomorpholin-2-yl)acetic acid 
• 1429385-28-3 (5R,6R)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-4-((S)-1-(ethylthio)butan-2-yl)morpholin-3-one 
• 1574556-50-5 C₂₆H₂₉Cl₂NO₃S 
• 1574556-51-6 C₂₆H₂₉Cl₂NO₃S 
• 1574556-38-9 C₃₂H₃₅Cl₂FN₂O₄S 
• 1574556-39-0 C₃₂H₃₅Cl₂FN₂O₄S 
• 1574556-35-6 C₃₂H₃₂Cl₂F₂N₂O₄S 
• 1574556-37-8 C₃₂H₃₂Cl₂F₂N₂O₄S 
• 1574556-32-3 C₃₂H₃₃Cl₂FN₂O₄S 
• 1574556-33-4 C₃₂H₃₃Cl₂FN₂O₄S 
• 1429388-21-5 C₃₂H₃₃Cl₂FN₂O₄S 
• 1429388-22-6 C₃₂H₃₃Cl₂FN₂O₄S 
• 1574556-28-7 C₃₂H₃₄Cl₂N₂O₄S 

Relevant academic research and scientific papers

Selective and potent morpholinone inhibitors of the MDM2-p53 protein-protein interaction

We previously reported the discovery of AMG 232, a highly potent and selective piperidinone inhibitor of the MDM2-p53 interaction. Our continued search for potent and diverse analogues led to the discovery of novel morpholinone MDM2 inhibitors. This change to a morpholinone core has a significant impact on both potency and metabolic stability compared to the piperidinone series. Within this morpholinone series, AM-8735 emerged as an inhibitor with remarkable biochemical potency (HTRF IC50 = 0.4 nM) and cellular potency (SJSA-1 EdU IC50 = 25 nM), as well as pharmacokinetic properties. Compound 4 also shows excellent antitumor activity in the SJSA-1 osteosarcoma xenograft model with an ED50 of 41 mg/kg. Lead optimization toward the discovery of this inhibitor as well as key differences between the morpholinone and the piperidinone series will be described herein.

HETEROCYCLIC COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER

The present invention provides MDM2 inhibitor compounds of Formula I or II, or the pharmaceutically acceptable salts thereof, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.