70415-85-9Relevant articles and documents
Design, synthesis and biological evaluation of novel 4-arylaminopyrimidine derivatives possessing a hydrazone moiety as dual inhibitors of L1196M ALK and ROS1
Wang, Yu,Zhang, Guogang,Hu, Gang,Bu, Yanxin,Lei, Hongrui,Zuo, Daiying,Han, Mengting,Zhai, Xin,Gong, Ping
, p. 80 - 89 (2016)
A series of 4-arylaminopyrimidine derivatives possessing a hydrazone moiety were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against ALK-addicted KARPAS299 and ROS1-addicted HCC78, while also showing much less potent activity against A549, H460 and HT-29, whose growth were not dependent on ALK and/or ROS1, as compared with crizotinib and ceritinib. The most promising compound, 7b, showed high antiproliferative effects on ALK-addicted KARPAS299 and ROS1-addicted HCC78?cell lines with IC50of 20?nM and 28?nM, respectively, but showed no inhibitory activity against A549, H460 and HT-29. The enzymatic assay identified 7b as a potent and selective ALK and ROS1 dual inhibitor with IC50of 2.5?nM and 2.7?nM, respectively. It also exhibited good inhibitory activity against the L1196M ALK with an IC50value of 67?nM.
Fragment-based modification of 2,4-diarylaminopyrimidine derivatives as ALK and ROS1 dual inhibitors to overcome secondary mutants
Chen, Yuxiang,Guo, Ming,Li, Tong,Li, Wei,Wei, Shangfei,Zhai, Xin,Zhao, Tianming,Zhu, Minglin
, (2020/09/01)
In order to explore novel ALK and ROS1 dual inhibitors capable of overcoming crizotinib-resistant mutants, two series of 2,4-diarylaminopyrimidine derivatives were designed, synthesized and evaluated for their in vitro cytotoxic activity. In this work, we retained the 2,4-diarylaminopyrimidine scaffold and derivatize the DAAP scaffold with sulfonyl and acrylamide moieties to extend the structure–activity relationship (SAR) study. To our delight, some compounds exhibited excellent inhibitory activity with a double-digit nanomolar level in MTT assay. Four compounds were selected for enzymic assays further, the results led to the identification of a potent ALK and ROS1 dual inhibitor X-17, with IC50 values of 3.7 nM, 2.3 nM, 8.9 nM and 1.9 nM against ALK, ALKL1196M, ALKG1202R and ROS1, respectively. Ultimately, the molecular docking studies on X-17 clearly disclosed reasonable and optimal binding interactions with ALK.
The novel anti-tumor medicine synthetic method and a pharmaceutically acceptable salt thereof and solid preparation (by machine translation)
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Paragraph 0035; 0036, (2018/09/08)
The invention discloses a method for synthesis of antineoplastic agent, the chemical name is 5 - chloro - N2 - (3 - amino-acetyl aminophenyl) - N4 - (2 - [...] phenyl) pyrimidine - 2, 4 - diamine. At the same time, its salt, crystalline form research, select and suitable for further development as a preparation of the maleate, tartrate and succinate and its corresponding crystalline form. The invention also provides a to the antineoplastic agent as the active ingredient of the solid preparation, wherein the supplemented with one or more solubilising. The invention solid preparation dissolution characteristic and excellent stability, with clinical application prospect. (by machine translation)
