Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRAFV600E and VEGFR-2 dual inhibitors was written by Wang, Yuanyuan;Wan, Shanhe;Li, Zhonghuang;Fu, Yu;Wang, Guangfa;Zhang, Jiajie;Wu, Xiaoyun. And the article was included in European Journal of Medicinal Chemistry in 2018.Application of 103-16-2 The following contents are mentioned in the article:
Aiming to explore novel BRAFV600E and VEGFR-2 dual inhibitors, a series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and biol. evaluated. Most of the synthesized 1H-pyrazolo[3,4-d]pyrimidine compounds displayed moderate to high potent activity in both enzymic and cellular proliferation assays. Among these compounds, N-(4-chlorophenyl)-1-methyl-5-((1-methyl-1H-pyrazolo [3,4-d]pyrimidin-4-yl)oxy)-1H-benzo[d]imidazol-2-amine, 1-methyl-5-((1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl) oxy)-N-(p-tolyl)-1H-benzo[d]imidazol-2-amine, N-(4-bromophenyl)-1-methyl-5-((1-methyl-1H-pyrazolo [3,4-d]pyrimidin-4-yl)oxy)-1H-benzo[d]imidazol-2-amine and 1-methyl-5-((1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl) oxy)-N-(4-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-2-amine showed remarkably high inhibitory activities against both BRAFV600E and VEGFR-2 kinase comparable to pos. control Sorafenib. Particularly, compound 1-methyl-5-((1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl) oxy)-N-(4-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-2-amine also showed potent anti-proliferative activity against BRAFV600E-expressing A375 (IC50 = 1.74 μM) and H-29 (IC50 = 6.92 μM) as well as VEGFR-2-expressing HUVEC (IC50 = 5.89 μM), which was also comparable to Sorafenib. Furthermore, kinase selectivity profile showed that 1-methyl-5-((1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl) oxy)-N-(4-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-2-amine had almost poor or no significant inhibitory activity against wild-type BRAF and 15 other tested protein kinases. Flow cytometric anal. showed that compound 1-methyl-5-((1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl) oxy)-N-(4-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-2-amine mainly arrested the A375 and HUVEC cell lines in the G0/G1 stage with a concentration-dependent effect. In addition, the mol. docking and mol. dynamics simulations suggested that 1-methyl-5-((1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl) oxy)-N-(4-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-2-amine adopted a similar binding pattern with Sorafenib at the ATP-binding sites of BRAFV600E and VEGFR-2. Taken together, these results indicated that compound 1-methyl-5-((1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl) oxy)-N-(4-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazol-2-amine may serve as novel lead compound in research on more effective BRAFV600E and VEGFR-2 dual inhibitors. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2Application of 103-16-2).
4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials.Application of 103-16-2
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem