127033-74-3Relevant articles and documents
Discovery of new thieno[3,2-d]pyrimidine derivatives targeting EGFRL858R/T790M NSCLCs by the conformation constrained strategy
Chen, Yang,Cheng, Zhongyu,Huang, Xin,Jiang, Yaoxuan,Qiao, Hui,Xie, Jiahao,Yang, Linlin,Yu, Bin,Zhao, Wen,Zhou, Wenjuan
, (2020)
Studies on the third-generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFRL858R/T790M mutant remain hotspots, specifically for non-small cell lung cancer (NSCLC). In the current study, a new series of EGFR-TKIs with thieno[3,2-d]pyrimidine derivatives(6a-6r) bearing quinolin-2(1H)-ones were designed and synthesized, through conformational constrained strategy from the third generation of EGFR-TKI olmutinib. In vitro structure-activity relationship (SAR) studies indicated that compounds 6a, 6l, 6m, 6n and 6o exhibited good selective inhibition to EGFRL858R/T790M (IC50 ≤ 250 nM) over wild type EGFR (IC50 > 10000 nM). The observed selectivity of compounds 6l and 6o was also proved by the computational molecular docking and the cellular thermal shift assay. These compounds had good growth inhibitory effect on the four tested cancer cell lines. Specifically, 6o could significantly inhibit the colony formation, wound healing and the expression of p-EGFR and its downstream p-ERK in EGFRL858R/T790M H1975 lung cancer cells. Our findings suggest that the thieno[3,2-d]pyrimidine compounds, especially 6l and 6o, can selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs.
A 7 - hydroxy -2 - quinolinone of preparation method
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Paragraph 0044; 0045, (2019/06/07)
The invention discloses a formula I compound represented by the preparation method, the method comprises the following steps: in a solvent, in the arrowhead class under the action of the catalyst, on the compound II are shown in the following of the dehydrogenation reaction to obtain the compound I can be. Preparation method of this invention has the following advantages: the raw materials used are cheap, product yield and high purity, the purity of 98% or more, the color white and non-heterogeneous, after treatment is simple, catalyst and solvent can be recycled, wastes very little, for environmental protection, it is suitable for industrial production.
A process for preparing 7 - hydroxy - 2 - quinolinone of the method (by machine translation)
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Paragraph 0036; 0037, (2017/10/06)
The invention discloses a process for preparing 7 - hydroxy - 2 - quinolinone of the method, specific steps are as follows: in the organic solvent, 3, 4 - dihydro - 7 - hydroxy - 2 - quinolone in the catalysis of DDQ heating dehydrogenation, to get the 7 - hydroxy - 2 - quinolinone. The operation is simple, mild reaction conditions, raw materials are easy, simple and efficient, pervasive is good. (by machine translation)
