1394939-93-5

Basic information

• Product Name: 2,6-difluoro-N-{3-[5-(pyridin-4-yl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}benzenesulfonamide
• Synonyms: 2,6-difluoro-N-{3-[5-(pyridin-4-yl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}benzenesulfonamide
• CAS NO: 1394939-93-5
• Molecular Weight: 513.589
• Mol File: 1394939-93-5.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 2,6-difluoro-N-{3-[5-(pyridin-4-yl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}benzenesulfonamide(CAS DataBase Reference)
• NIST Chemistry Reference: 2,6-difluoro-N-{3-[5-(pyridin-4-yl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}benzenesulfonamide(1394939-93-5)
• EPA Substance Registry System: 2,6-difluoro-N-{3-[5-(pyridin-4-yl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}benzenesulfonamide(1394939-93-5)

Safety Data

• Hazardous Substances Data: 1394939-93-5(Hazardous Substances Data)

Upstream product

• 344329-76-6 tetrahydro-pyran-4-carboxylic acid amide 
• 1394939-89-9 5-bromo-4-(3-nitrophenyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazole 
• 88571-77-1 tetrahydro-2H-pyran-4-carbothioamide 
• 1394939-91-3 3-[5-(pyridin-4-yl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]aniline 
• 60230-36-6 2,6-difluorobenzene-1-sulfonyl chloride 
• 1394939-90-2 4-[4-(3-nitrophenyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-5-yl]pyridine 
• 1394939-88-8 4-(3-nitrophenyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazole 
• 110238-91-0 tetrahydropyran-4-carboxylic acid methyl ester 
• 2227-64-7 3'-nitro-2-bromoacetophenone 

Relevant articles and documents

Optimization of diarylthiazole B-Raf inhibitors: Identification of a compound endowed with high oral antitumor activity, mitigated hERG inhibition, and low paradoxical effect

Aberrant activation of the mitogen-activated protein kinase (MAPK)-mediated pathway components, RAF-MEK-ERK, is frequently observed in human cancers and clearly contributes to oncogenesis. As part of a project aimed at finding inhibitors of B-Raf, a key player in the MAPK cascade, we originally identified a thiazole derivative endowed with high potency and selectivity, optimal in vitro ADME properties, and good pharmacokinetic profiles in rodents, but that suffers from elevated hERG inhibitory activity. An optimization program was thus undertaken, focused mainly on the elaboration of the R1 and R2 groups of the scaffold. This effort ultimately led to N-(4-{2-(1-cyclopropylpiperidin-4-yl)-4-[3-(2,5-difluorobenzenesulfonylamino)-2-fluorophenyl]thiazol-5-yl}-pyridin-2-yl)acetamide (20), which maintains favorable in vitro and in vivo properties, but lacks hERG liability. Besides exhibiting potent antiproliferative activity against only cell lines bearing B-Raf V600E or V600D mutations, compound 20 also intriguingly shows a weaker "paradoxical" activation of MEK in non-mutant B-Raf cells than other known B-Raf inhibitors. It also demonstrates very good efficacy in vivo against the A375 xenograft melanoma model (tumor volume inhibition >90% at 10 mg kg-1); it is therefore a suitable candidate for preclinical development.

THIAZOLYLPHENYL-BENZENESULFONAMIDO DERIVATIVES AS KINASE INHIBITORS

Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.