1099669-23-4Relevant academic research and scientific papers
Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design
Wang, Linxiao,Zhang, Qian,Wang, Zhe,Zhu, Wufu,Tan, Ninghua
, (2021)
Using cheminformatics tools RDKit and literature investigation, four series of 24 thienopyrimidine/N-methylpicolinamide derivatives substituted with pyrimidine were designed, synthesized and evaluated for activities against three cancer cell lines (MDA-MB-231, HCT116 and A549), TAK1 kinase and NF-κB signaling pathway. Almost all compounds showed selectivity toward the A549 cell lines and the most promising compound 38 could inhibit TAK1 kinase and NF-κB signaling pathway with the IC50 values of 0.58 and 0.84 μM. Moreover, 38 can induce cell cycle arrest of A549 cells at the G2/M checkpoint with 30.57% and induce apoptosis (34.94%) in a concentration-dependent manner. And western blot showed that compound 38 could inhibit TNF-α-induced IκBα phosphorylation, IκBα degradation, p65 phosphorylation and TAK1 phosphorylation, and reduce the expression of p65. What's more, the studies of docking, molecular dynamics, MM/PBSA and frequency analysis theoretically supported the conclusions of the bioevaluation.
Synthesis and bioevaluation study of novel N-methylpicolinamide and thienopyrimidine derivatives as selectivity c-Met kinase inhibitors
Wang, Linxiao,Xu, Shan,Chen, Xiuying,Liu, Xiaobo,Duan, Yongli,Kong, Dejia,Zhao, Dandan,Zheng, Pengwu,Tang, Qidong,Zhu, Wufu
, p. 245 - 256 (2017/12/06)
Four series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing pyridazinone were designed and synthesized and evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds were
Preparation and application of thiophene pyrimindine compound containing heteroaryl amide structure
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Paragraph 0101; 0102; 0109; 0110, (2017/10/25)
The invention relates to a thiophene pyrimindine compound containing a heteroaryl amide structure shown in the general formula I, and a pharmaceutically acceptable salt, an aquo-complex, a solvate and a predrug of the thiophene pyrimindine compound containing the heteroaryl amide structure, wherein the implications of the substituent group R1, X, Y, D and Z are shown in the description. The invention further relates to a strong effect of inhibiting c-Met kinase of the compound shown in the general formula I, and also relates to application of the compound and the pharmaceutically acceptable salt, the aquo-complex, the solvate and the predrug of the thiophene pyrimindine compound to preparing a medicine used for treating diseases caused by abnormal high expression of the c-Met kinase, particularly application to preparing a medicine for treating and/or preventing cancers.
