1380228-53-4

Basic information

• Product Name: N-(3-(3-(9H-purin-6-yl)pyridin-2-ylamino)-2,4-difluorophenyl)benzenesulfonamide
• Synonyms: N-(3-(3-(9H-purin-6-yl)pyridin-2-ylamino)-2,4-difluorophenyl)benzenesulfonamide
• CAS NO: 1380228-53-4
• Molecular Weight: 479.47
• Mol File: 1380228-53-4.mol

Chemical Properties

• CAS DataBase Reference: N-(3-(3-(9H-purin-6-yl)pyridin-2-ylamino)-2,4-difluorophenyl)benzenesulfonamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(3-(3-(9H-purin-6-yl)pyridin-2-ylamino)-2,4-difluorophenyl)benzenesulfonamide(1380228-53-4)
• EPA Substance Registry System: N-(3-(3-(9H-purin-6-yl)pyridin-2-ylamino)-2,4-difluorophenyl)benzenesulfonamide(1380228-53-4)

Safety Data

• Hazardous Substances Data: 1380228-53-4(Hazardous Substances Data)

Upstream product

• 5509-65-9 2,6-difluoroaniline 
• 946826-47-7 N-(3-amino-2,6-difluorophenyl)acetamide 
• 1380229-14-0 N-(2,4-difluoro-3-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)benzenesulfonamide 
• 535170-20-8 tert-butyl (3-amino-2,6-difluorophenyl)carbamate 
• 535170-17-3 tert-butyl (2,6-difluoro-3-nitrophenyl)carbamate 
• 83141-10-0 2,6-difluoro-3-nitrobenzoic acid 
• 1380228-73-8 2,6-difluoro-N₁-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)benzene-1,3-diamine 
• 1380228-71-6 benzyl 2,4-difluoro-3-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl carbamate 
• 1093101-52-0 6-(2-fluoropyridin-3-yl)-9-(tetrahydro-2-hydro-pyran-2-yl)-9H-purine 
• 1269421-42-2 N-(3-amino-2,4-difluorophenyl)benzenesulfonamide 
• 25892-08-4 N-(2,6-difluoro-3-nitrophenyl)acetamide 
• 3896-29-5 N-(2,6-difluorophenyl)acetamide 
• 7306-68-5 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 
• 1380228-68-1 benzyl tert-butyl (2,4-difluoro-1,3-phenylene)dicarbamate 

Relevant articles and documents

Protein kinase inhibitor and its composition and use thereof

The invention relates to compounds as shown in the general formula (I), pharmaceutical compositions containing the compounds, a method for treating diseases and disease symptoms related to abnormal activity of protein kinase by using the compounds, and medicinal use of the compounds.

Discovery of a highly specific and potent pan-RAF inhibitor

We describe the structure-based design and synthesis of N-(2,6-difluorophenyl)-3-(9H-purin-6-yl)pyridine-2-amine derivatives as a selective pan-RAF kinase inhibitor. The synthesized compounds showed highly potent and specific inhibition of the BRAFV600E mutant cell line. Among them, N-(3-((3-(9H-purin-6-yl) pyridine-2-yl)amino)-2,4-difluorophenyl)furan-3-sulfonamide (4b) exhibited the most potent inhibitory activities against protein kinase enzymes BRAFV600E, BRAFWT, and CRAF (IC50 of 2, 2, and 1 nM, respectively) and a mutant cell line bearing a BRAFV600E mutation, A375P (GI50 of 7 nM).

Purinylpyridinylamino-based DFG-in/αC-helix-out B-Raf inhibitors: Applying mutant versus wild-type B-Raf selectivity indices for compound profiling

One of the challenges for targeting B-RafV600E with small molecule inhibitors had been achieving adequate selectivity over the wild-type protein B-RafWT, as inhibition of the latter has been associated with hyperplasia in normal tissues. Recent studies suggest that B-Raf inhibitors inducing the 'DFG-in/αC-helix-out' conformation (Type IIB) likely will exhibit improved selectivity for B-RafV600E. To explore this hypothesis, we transformed Type IIA inhibitor (1) into a series of Type IIB inhibitors (sulfonamides and sulfamides 4-6) and examined the SAR. Three selectivity indices were introduced to facilitate the analyses: the B-RafV600E/B-RafWT biochemical (bS), cellular (cS) selectivity, and the phospho-ERK activation (pA). Our data indicates that α-branched sulfonamides and sulfamides show higher selectivities than the linear derivatives. We rationalized this finding based on analysis of structural information from the literature and provided evidence for a monomeric B-Raf-inhibitor complex previously hypothesized to be responsible for the desired B-RafV600E selectivity.

NOVEL PURINYLPYRIDINYLAMINO-2,4-DIFLUOROPHENYL SULFONAMIDE DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION WITH INHIBITORY ACTIVITY AGAINST RAF KINASE, CONTAINING SAME AS ACTIVE INGREDIENT

A novel purinylpyridinylamino-2,4-difluorophenyl sulfonamide derivative, a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition with an inhibitory activity against Raf kinase, containing the same as an active ingredient are provided. The purinylpyridinylamino-2,4-difluorophenyl sulfonamide derivative of the present invention effectively regulates the activity of B-Raf kinase, and thus may be useful for preventing or treating cancers induced by the over-activation of Raf kinase, especially various melanoma, colorectal cancer, prostate cancer, thyroid cancer, ovarian cancer and the like.

KINASE MODULATING COMPOUNDS, COMPOSITIONS CONTAINING THE SAME AND USE THEREOF

The invention provides a compound represented by formula (I) which may modulate a kinase, and a pharmaceutical composition thereof, as well as the method for preventing or treating a protein kinase mediated disease or condition.