1309685-87-7

Upstream product

• 16292-95-8 4-nitro-3-methoxyphenol 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 1309685-88-8 tert-butyl[2-(3-methoxy-4-nitrophenoxy)ethoxy]dimethylsilane 

Downstream Products

• 1309685-90-2 (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'-carboxylic acid [4-(2-hydroxyethoxy)-2-methoxyphenyl]amide 
• 1366097-82-6 (2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid {4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-2-methoxy-phenyl}-amide 
• 1366097-14-4 (3R,5'S,7'S,7a'R)-6-chloro-7'-(3-chloro-2-fluorophenyl)-2'-[4-(2-hydroxyethoxy)-2-methoxyphenyl]-5'-(2,2-dimethyl-propyl)-2',3',7',7a'-tetrahydrospiro[indoline-3,6'-pyrrolo[1,2-c]imidazole]-1',2(5'H)-dione 
• 1360821-65-3 rac-(2S,3R,4R,5R)-2'-chloro-4-(3-chloro-2-fluorophenyl)-N-(4-(2-hydroxyethoxy)-2-methoxyphenyl)-2-neopentyl-5'-oxo-4',5'-dihydrospiro[pyrrolidine-3,6'-thieno[3,2-b]pyrrole]-5-carboxamide 
• 1360822-25-8 (2R,3S,4S,5S)-2'-chloro-4-(3-chloro-2-fluorophenyl)-N-(4-(2-hydroxyethoxy)-2-methoxyphenyl)-2-neopentyl-5'-oxo-4',5'-dihydrospiro[pyrrolidine-3,6'-thieno[3,2-b]pyrrole]-5-carboxamide 
• 1345866-74-1 (2'R,3'S,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid [4-(2-hydroxy-ethoxy)-2-methoxy-phenyl]-amide 
• 1309685-91-3 (2'R,3'S,4'R,5'S)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid [4-(2-hydroxy-ethoxy)-2-methoxy-phenyl]amide 

Relevant academic research and scientific papers

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.

Substituted Heteroaryl Spiropyrrolidine MDM2 Antagonists

There are provided compounds of the general formula wherein A, B, V, W, R1, R2, R3, R3, and R4, are as described herein and enantiomers and pharmaceutically acceptable salts thereof. The compounds are useful as anticancer agents.

Substituted Spiro[3H-Indole-3,6'(5'H)-[1H]Pyrrolo[1,2c]Imidazole-1',2(1H,2'H)-diones

There are provided compounds of the formula wherein X, Y, R1, R1′, R2, R2′, R3, R4, R5 and R6 are as described herein and enantiomers or a pharmaceutically acceptable salt or ester thereof. The compounds are useful as anticancer agents.

SPIROINDOLINONE PYRROLIDINES

There are provided compounds of the formula wherein X, Y and R1 to R8 are described herein along with the enantiomers, pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

SPIROINDOLINONE PYRROLIDINES

There are provided compounds of the formula (I) wherein X, Y and R1 to R8 are as described herein, their enantiomers and pharmaceutically acceptable salts and esters, as well as processes for making these compounds and medicaments containing them.