5399-92-8Relevant articles and documents
Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRAFV600E and VEGFR-2 dual inhibitors
Wang, Yuanyuan,Wan, Shanhe,Li, Zhonghuang,Fu, Yu,Wang, Guangfa,Zhang, Jiajie,Wu, Xiaoyun
, p. 210 - 228 (2018/06/12)
Aiming to explore novel BRAFV600E and VEGFR-2 dual inhibitors, a series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and biologically evaluated in this study. Most of the synthesized 1H-pyrazolo[3,4-d]pyrimidine compounds displayed moderate to high potent activity in both enzymatic and cellular proliferation assays. Among these compounds, 9e, 9g, 9m and 9u showed remarkably high inhibitory activities against both BRAFV600E and VEGFR-2 kinase comparable to positive control Sorafenib. Particularly, compound 9u 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 9u had almost poor or no significant inhibitory activity against wild-type BRAF and 15 other tested protein kinases. Flow cytometric analysis showed that compound 9u mainly arrested the A375 and HUVEC cell lines in the G0/G1 stage with a concentration-dependent effect. In addition, the molecular docking and molecular dynamics simulations suggested that 9u adopted a similar binding pattern with Sorafenib at the ATP-binding sites of BRAFV600E and VEGFR-2. Taken together, these results indicated that compound 9u may serve as novel lead compound in research on more effective BRAFV600E and VEGFR-2 dual inhibitors.
(1H-pyrazolo[3,4-d]pyrimidine)-4-amino derivative and application of same as IDO inhibitor to drug preparation
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Paragraph 0049; 0050, (2017/08/31)
The invention discloses a (1H-pyrazolo[3,4-d]pyrimidine)-4-amino derivative and a preparation method thereof, and application of the derivative as an IDO inhibitor. The derivative provided by the invention can be used for preventing and/or treating a plurality of diseases, such as Alzheimer's disease, cataract, infections related to cellular immune activation, autoimmune diseases, AIDS, cancers, depression or metabolic disorder of tryptophan.
1-(2-tetrahydropyrane)-1H-pyrazole[3, 4-d] pyrimidine compound having anti-tumor activity and preparation method thereof
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Paragraph 0049; 0050; 0051; 0052, (2017/08/28)
The invention discloses a 1-(2-tetrahydropyrane)-1H-pyrazole[3, 4-d] pyrimidine compound having anti-tumor activity. A general formula of the compound is shown as follows. The invention further discloses a synthesis method of the compound and a medicinal composition containing the compound. The invention further discloses application of the medicinal composition in treating diseases caused by protein kinase activity abnormality. The pyrazole [3, 4-d] pyrimidine compound which is novel in structure and remarkable in anti-tumor activity is developed. The compound can be used as a double-target inhibitor of BRAF/VEGFR-2 kinase and has good effect and wide application prospect in the aspect of treating the diseases caused by protein kinase activity abnormality.