1239611-22-3

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 53994-85-7 (±)-2-(tert-butoxycarbonyl)-2-(4-chlorophenyl)acetic Acid 
• 6212-33-5 2-(4-Chlorophenyl)glycine 

Downstream Products

• 1429382-50-2 (±)-tert-butyl 2-(3-chlorophenyl)-1-(4-chlorophenyl)-2-oxoethylcarbamate 
• 1432669-51-6 (R)-2-((2S,5R,6S)-2-(4-fluorobenzyl)-5,6-bis(4-chlorophenyl)-3-oxomorpholino)pentanoic acid 
• 1432669-60-7 2-((2R,5S,6R)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-4-(cyclopropylmethyl)-3-oxomorpholin-2-yl)acetic acid 
• 1432669-57-2 2-((2S,5R,6S)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-4-(cyclopropylmethyl)-3-oxomorpholin-2-yl)acetic acid 
• 1432669-78-7 (R)-ethyl 2-((2S,3R)-2,3-bis(4-chlorophenyl)-5-oxomorpholino)pentanoate 
• 1432669-80-1 (R)-ethyl 2-((2S,5R,6S)-2-(4-fluorobenzyl)-5,6-bis(4-chlorophenyl)-3-oxomorpholino)pentanoate 

Relevant academic research and scientific papers

CIS-MORPHOLINONE AND OTHER COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER

The present invention provides MDM2 inhibitor compounds of Formula (I), 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.

Rational design and binding mode duality of MDM2-p53 inhibitors

Structural analysis of both the MDM2-p53 protein-protein interaction and several small molecules bound to MDM2 led to the design and synthesis of tetrasubstituted morpholinone 10, an MDM2 inhibitor with a biochemical IC 50 of 1.0 μM. The cocrystal structure of 10 with MDM2 inspired two independent optimization strategies and resulted in the discovery of morpholinones 16 and 27 possessing distinct binding modes. Both analogues were potent MDM2 inhibitors in biochemical and cellular assays, and morpholinone 27 (IC50 = 0.10 μM) also displayed suitable PK profile for in vivo animal experiments. A pharmacodynamic (PD) experiment in mice implanted with human SJSA-1 tumors showed p21WAF1 mRNA induction (2.7-fold over vehicle) upon oral dosing of 27 at 300 mg/kg.