1380227-96-2

Upstream product

• 1380228-66-9 N-(3-amino-2,4-difluorophenyl)propane-2-sulfonamide 
• 25892-08-4 N-(2,6-difluoro-3-nitrophenyl)acetamide 
• 3896-29-5 N-(2,6-difluorophenyl)acetamide 
• 5509-65-9 2,6-difluoroaniline 
• 946826-47-7 N-(3-amino-2,6-difluorophenyl)acetamide 
• 7306-68-5 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 
• 1380228-65-8 tert-butyl 2,6-difluoro-3-(1-methylethylsulfonamido)phenylcarbamate 
• 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 
• 87-42-3 6-chloropurine 
• 1380228-67-0 N-(2,4-difluoro-3-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)propan-2-sulfonamide 
• 260552-98-5 2,6-difluoro-3-nitrobenzoic acid chloride 
• 1093101-52-0 6-(2-fluoropyridin-3-yl)-9-(tetrahydro-2-hydro-pyran-2-yl)-9H-purine 

Relevant academic research and scientific papers

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.