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• 1419186-30-3 4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-3-methoxybenzoic acid methyl ester 
• 1345866-84-3 4-{[(2'R,3'S,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-3-methoxybenzoic acid methyl ester 
• 1398571-87-3 (3′S,4′R,7′S,8′S,8a′R)-6″-chloro-8′-(3-chloro-2-fluorophenyl)-3′,4′-diphenyl-3′,4′,8′,8a′-tetrahydro-1′H-dispiro-[cyclohexane-1,6′-pyrrolo[2,1-c][1,4]oxazine-7′,3″-indoline]-1′,2″-dione 

Relevant academic research and scientific papers

MDM2 DEGRADERS AND USES THEREOF

The present invention relates to compounds and methods useful for the modulation of mouse double minute 2 homolog ("MDM2") protein via ubiquitination and/or degradation by compounds according to the present invention.

SPIROCYCLIC INDOLONE POLYETHYLENE GLYCOL CARBONATE COMPOUND, COMPOSITION, PREPARATION METHOD AND USE THEREOF

The present invention relates to a spirocyclic indolone polyethylene glycol carbonate compound, a composition thereof, a preparation method therefor, and a use thereof as an anticancer drug due to the antitumor activity thereof. The structural formula of the spirocyclic indolone polyethylene glycol carbonate compound is shown below. The compound has excellent tumor inhibitory activity, water solubility, low toxicity, and can be used for intravenous injection.

Spiroindolone polyethylene glycol carbonate compound, and compositions, preparation method and application thereof

The invention relates to a spiroindolone polyethylene glycol carbonate compound, compositions and a preparation method thereof, and an application of the spiroindolone polyethylene glycol carbonate compound as an anticancer drug due to antitumor activity of the spiroindolone polyethylene glycol carbonate compound. The spiroindolone polyethylene glycol carbonate compound has a structural formula asdescribed in the specification, has excellent tumor suppressive activity, good water solubility and low toxicity, and can be used for intravenous injections.

Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy

The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994.

Synthesis of a spiroindolinone pyrrolidinecarboxamide MDM2 antagonist

A practical synthesis of a spiroindolinone pyrrolidinecarboxamide MDM2 antagonist 2 is reported. Cycloaddition of dipolarophile 3 with imine 30 afforded a complex mixture of diastereomers that were isomerized to the desired stereoisomer 31 by heating the mixture in the presence of DBU. After hydrolysis, the resulting product was resolved with a chiral amine to give an enantiopure acid which was converted to the target product 2. The process has been scaled up to a multihundred-gram scale. In addition, an asymmetric synthesis of 31 catalyzed by AgOAc and a chiral phosphine ligand was developed to give enantiomerically enriched 31, which was also converted to enantiopure 2.

SPIRO-OXINDOLE MDM2 ANTAGONISTS

Provided herein are compounds, compositions, and methods in the field of medicinal chemistry. The compounds and compositions provided herein relate to spiro-oxindoles which function as antagonists of the interaction between p53 and MDM2, and their use as

SPIRO-OXINDOLE MDM2 ANTAGONISTS

Provided herein are compounds, compositions, and methods in the field of medicinal chemistry. The compounds and compositions provided herein relate to spiro-oxindoles which function as antagonists of the interaction between p53 and MDM2, and their use as therapeutics for the treatment of cancer and other diseases.

Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction

We report herein the design of potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. Compound 5 binds to MDM2 with a K i of 0.6 nM, activates p53 at concentrations as low as 40 nM, and potently and selectively inhibits

SMALL MOLECULE INHIBITORS OF MDM2 AND USES THEREOF

The invention relates to small molecules which function as inhibitors of the interaction between p53 and MDM2. The invention also relates to the use of these compounds for inhibiting cell growth, inducing cell death, inducing cell cycle arrest and/or sens