1384513-06-7

Upstream product

• 141-97-9 ethyl acetoacetate 
• 696-41-3 m-iodobenzaldehyde 
• 1384513-05-6 ethyl 2-acetyl-4-(4-chlorophenyl)-3-(3-iodophenyl)-4-oxobutanoate 
• 74-89-5 methylamine 

Downstream Products

• 1384513-14-7 5-(4-chlorophenyl)-1,2-dimethyl-4-(3-(4-(4-nitrophenyl)-piperazin-1-yl)phenyl)-1H-pyrrole-3-carboxylic acid 
• 1384513-18-1 5-(4-chlorophenyl)-4-(3-(4-(4-(4-fluoro-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1,2-dimethyl-1H-pyrrole-3-carboxylic acid 
• 1384512-98-4 (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1,2-dimethyl-1H-pyrrole-3-carboxylic acid 
• 1384513-10-3 5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethyl-N-(3-(4-methylpiperazin-1-yl)propyl)-1H-pyrrole-3-carboxamide 
• 1384512-95-1 (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(((4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)phenyl)-1,2-dimethyl-N-(3-(4-methylpiperazin-1-yl)propyl)-1H-pyrrole-3-carboxamide 
• 1384512-96-2 (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1,2-dimethyl-N-(3-(4-methylpiperazin-1-yl)propyl)-1H-pyrrole-3-carboxamide 
• 1384512-97-3 (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenylsulfonamido)-phenyl)piperazin-1-yl)phenyl)-N,1,2-trimethyl-1H-pyrrole-3-carboxamide 
• 1384512-99-5 (R)-N-(4-(4-(3-(2-(4-chlorophenyl)-1,5-dimethyl-1H-pyrrol-3-yl)phenyl)piperazin-1-yl)phenyl)-4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrobenzenesulfonamide 
• 1305320-66-4 5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethyl-1H-pyrrole-3-carboxylic acid 
• 1391108-32-9 5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethyl-1H-pyrrole-3-carbonitrile 
• 1391108-30-7 3-chloro-5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethyl-1H-pyrrole 
• 1391108-29-4 2-(4-chlorophenyl)-3-(3-iodophenyl)-1,5-dimethyl-1H-pyrrole 
• 1428145-89-4 5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethyl-N-(methylsulfonyl)-1H-pyrrole-3-carboxamide 
• 1391108-31-8 5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethyl-1H-pyrrole-3-carboxamide 

Relevant academic research and scientific papers

A potent and highly efficacious Bcl-2/Bcl-xL inhibitor

Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with Ki values of 50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.

Structure-based design of potent Bcl-2/Bcl-xL inhibitors with strong in vivo antitumor activity

Bcl-2 and Bcl-xL are key apoptosis regulators and attractive cancer therapeutic targets. We have designed and optimized a class of small-molecule inhibitors of Bcl-2 and Bcl-xL containing a 4,5-diphenyl-1H-pyrrole-3-carboxylic acid core structure. A 1.4 ?