620600-73-9

Upstream product

• 35623-11-1 3-(N-methylsulfamoyl)benzoic acid 
• 4025-64-3 3-Carboxybenzenesulfonyl chloride 

Downstream Products

• 132390-65-9 3-formyl-N-methyl-benzenesulfonamide 
• 1421506-04-8 (E)-3-(6-chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-N-methyl benzenesulfonamide 
• 1421506-44-6 (E)-3-(5-chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-N-methyl-benzenesulphonamide 
• 1421506-93-5 (E)-3-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-N-methyl-benzene-sulphonamide 
• 1421507-30-3 (Z)-3-(4,5-difluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-N-methyl-benzene-sulphonamide 

Relevant academic research and scientific papers

N'-Alkylaminosulfonyl Analogues of 6-Fluorobenzylideneindolinones with Desirable Physicochemical Profiles and Potent Growth Inhibitory Activities on Hepatocellular Carcinoma

The benzylideneindolinone 6-chloro-3-(3′-trifluoromethylbenzylidene)-1,3-dihydroindol-2-one (4) was reported to exhibit potent and selective growth inhibitory effects on hepatocellular carcinoma (HCC). Corroborative evidence supported multi-receptor tyrosine kinase (RTK) inhibition as a possible mode of action. However, the poor physicochemical properties of 4 limited its furtherance as a lead compound. In this study, the modification of 4 was investigated with the aim of improving its potency and physicochemical profile. The 6-fluorobenzylideneindolinone 3-12 bearing a 3′-N-propylaminosulfonyl substituent was found to be a promising substitute. Compound 3-12 [6-fluoro-3-(3′-N-propylaminosulfonylbenzylidene)-1,3-dihydroindol-2-one] was found to be tenfold more soluble than 4 and to have sub-micromolar growth inhibitory activities on HCC cells. It is apoptogenic and inhibits the phosphorylation of several RTKs in HuH7, of which the inhibition of FGFR4 and HER3 are prominent. Compound 3-12 decreased the tumor load in a physiologically relevant orthotopic HCC xenograft murine model. Structure-activity relationships support pivotal roles for the fluoro and N′-propylaminosulfonyl moieties in enhancing cell-based activity and moderating the physicochemical profile (solubility, permeability) of 3-12.

PHENETHANOLAMINE DERIVATIVES

The present invention relates to novel compounds of formula (I), or a salt, solvate, or physiologically functional derivative thereof, to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.