875765-02-9

Basic information

• Product Name: Benzenamine, 4-[[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy]-
• CAS NO: 875765-02-9
• Molecular Formula: C16H17N5O2
• Molecular Weight: 311.343
• Mol File: 875765-02-9.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: Benzenamine, 4-[[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy]-(CAS DataBase Reference)
• NIST Chemistry Reference: Benzenamine, 4-[[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy]-(875765-02-9)
• EPA Substance Registry System: Benzenamine, 4-[[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy]-(875765-02-9)

Safety Data

• Hazardous Substances Data: 875765-02-9(Hazardous Substances Data)

Upstream product

• 123-30-8 4-amino-phenol 
• 91446-15-0 4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]-pyrimidine 
• 5305-40-8 2,6-dichloro-pyrimidine carbaldehyde 
• 5399-92-8 4-chloro-1H-pyrazolo[3,4-d]pyrimidine 

Downstream Products

• 1423126-75-3 1-(4-((1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea 
• 1423126-60-6 1-(4-((1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)phenyl)-3-phenylurea 
• 1423126-48-0 1-(4-((1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)phenyl)-3-(2,3-dimethylphenyl)urea 

Relevant articles and documents

Bisarylureas based on 1H-Pyrazolo[3,4-d]pyrimidine Scaffold as Novel Pan-RAF inhibitors with potent anti-proliferative activities: Structure-based design, synthesis, biological evaluation & molecular modelling studies

RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures of BRAF (v-raf murine sarcoma viral oncogene homolog B1), starting from bisarylurea derivative based on 1H-pyrazolo[3,4-d]pyrimidine scaffold 1a. Most of the synthesized compounds showed good to excellent inhibitory activities against BRAFV600E kinase, possessed moderate to potent anti-proliferative activities against four tumor cell lines (A375, HT-29, PC-3 and A549) and good selectivity towards cancer cells rather normal cells (Madin-Darby canine kidney, MDCK). The most promising compound, 1v, exhibited potent inhibitory activity against not only BRAFV600E (half maximal inhibitory concentration, IC50 = 23.6 nM) but also wild-Type BRAF (IC50 = 51.5 nM) and C-RAF (IC50 = 8.5 nM), and effective cellular anti-proliferative activities against A375, HT-29, PC-3 and A549 cell lines as well as a very good selectivity profile. Moreover, compound 1v mainly arrested the A375 cell line in the G0/G1 stage, and showed significant suppression of MEK (mitogen-Activated protein kinase kinase) phosphorylation in A375 and HT-29 cell lines. Taken together, the optimal compound 1v showed excellent in vitro potency as a pan-RAF inhibitor. In addition, the promise of compound 1v was further confirmed by molecular dynamics simulation and binding free energy calculations.

C-MET MODULATORS AND METHOD OF USE

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