477573-39-0

Upstream product

• 20443-98-5 2,6-Dichlorobenzyl bromide 
• 199328-31-9 2-oxo-2,3-dihydro-1H-indole-5-sulfonyl chloride 
• 59-48-3 2-oxoindole 
• 1174006-95-1 5-chlorosulfonyl-indol-2-one 

Downstream Products

• 760997-82-8 3-{2-[5-(2,6-dichlorophenylmethanesulfonyl)-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-3-yl}propionic acid 
• 760998-00-3 5-(2,6-dichlorophenylmethanesulfonyl)-3-[1-[3-(3-hydroxypropyl)-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-2-yl]meth-(Z)-ylidene]-1,3-dihydroindol-2-one 
• 477574-82-6 (Z)-5-[{5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene}methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid 
• 477575-09-0 3-[1-[4-(4-Cyclopropylamino-piperidine-1-carbonyl)-3,5-dimethyl-1H-pyrrol-2-yl]-meth-(Z)-ylidene]-5-(2,6-dichloro-phenylmethanesulfonyl)-1,3-dihydro-indol-2-one 
• 1083096-72-3 (Z)-2-((5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene)methyl)-5-(2-(diethylamino)ethyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 
• 1083096-66-5 (Z)-2-((5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene)methyl)-3-methyl-5-(2-morpholinoethyl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 
• 1083096-68-7 (Z)-2-((5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene)methyl)-3-methyl-5-(2-(pyrrolidin-1-yl)ethyl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 
• 1083096-70-1 (Z)-2-((5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene)methyl)-3-methyl-5-(2-(piperidin-1-yl)ethyl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 
• 1083096-74-5 (R,Z)-2-((5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene)methyl)-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 
• 1235459-49-0 (Z)-5-(2,6-dichlorobenzylsulfonyl)-3-({3-[3-(diethylamino)propyl]-4-oxo-4,5,6,7-tetrahydro-1H-indol-2-yl}methylene)indolin-2-one 
• 1235459-50-3 (Z)-3-(2-{[5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene]methyl}-4-oxo-4,5,6,7-tetrahydro-1H-indol-3-yl)-N-[2-(diethylamino)ethyl]propanamide 
• 1235459-01-4 (Z)-3-(2-{[5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene]methyl}-4-oxo-4,5,6,7-tetrahydro-1H-indol-3-yl)-N-methylpropanamide 
• 1235459-42-3 (Z)-ethyl-3-(2-{[5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene]methyl}-4-oxo-4,5,6,7-tetrahydro-1H-indol-3-yl)propanoate 
• 1235458-26-0 (Z)-3-(2-{[5-(2,6-dichlorobenzylsulfonyl)-2-oxoindolin-3-ylidene]-methyl}-4-oxo-4,5,6,7-tetrahydro-1H-indol-3-yl)propanoic acid 

Relevant academic research and scientific papers

Rapid improvement of a reductive sulfonylation using design of experiment methods

Sulfone 2 was initially prepared using a zinc-mediated one-pot coupling procedure. A traditional sodium sulfite-mediated two-pot procedure was found to eliminate a major impurity, yet modest yields prevailed. Design of experiment methods with the aid of a basic parallel synthesizer rapidly led to a high-yielding one-pot process.

Mitochondrial-Targeting MET Kinase Inhibitor Kills Erlotinib-Resistant Lung Cancer Cells

Lung cancer cells harboring activating EGFR mutations acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) by activating several bypass mechanisms, including MET amplification and overexpression. We show that a significant proportion of activated MET protein in EGFR TKI-resistant HCC827 lung cancer cells resides within the mitochondria. Targeting the total complement of MET in the plasma membrane and mitochondria should render these cells more susceptible to cell death and hence provide a means of circumventing drug resistance. Herein, the mitochondrial targeting triphenylphosphonium (TPP) moiety was introduced to the selective MET kinase inhibitor PHA665752. The resulting TPP analogue rapidly localized to the mitochondria of MET-overexpressing erlotinib-resistant HCC827 cells, partially suppressed the phosphorylation (Y1234/Y1235) of MET in the mitochondrial inner membrane and was as cytotoxic and apoptogenic as the parent compound. These findings provide support for the targeting of mitochondrial MET with a TPP-TKI conjugate as a means of restoring responsiveness to chemotherapy.

PYRROLO-NITROGENOUS HETEROCYCLIC DERIVATIVES, THE PREPARATION AND THE PHARMACEUTICAL USE THEREOF

The invention provides new pyrrolo-nitrogenous heterocyclic derivatives represented by formula (I) or their salts, the preparation thereof, pharmaceutical compositions containing such derivatives and the use of such derivatives as therapeutic agents, espe

PYRROLO-NITROGENOUS HETEROCYCLIC DERIVATIES,THE PREPARATION AND THE PHARMCETICAL USE THEEOF

The invention provides new pyrrolo-nitrogenous heterocyclic derivatives represented by formula (I) or their salts, the preparation thereof, pharmaceutical compositions containing such derivatives and the use of such derivatives as therapeutic agents, especially as protein kinase inhibitors, wherein each substituent in formula (I) is same as defined in the description.

Hexahydro-cyclohepta-pyrrole oxindole as potent kinase inhibitors

The present invention is directed to a class indolinone compounds, hexahydro-cyclohepta-pyrrole oxindoles, which are useful as protein kinase inhibitors.

5-ARALKYSUFONYL-3-(PYRROL-2-YLMETHYLIDENE)-2-INDOLINONE DERIVATIVES AS KINASE INHIBITORS

The present invention relates to certain 5-aralkylsulfonyl-3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that inhibit kinases, in particular met kinase. Pharmaceutical compositions comprising these compounds, methods of treating diseases mediated by kinases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing them are also disclosed.