52753-44-3Relevant articles and documents
Design, synthesis and biological evaluation of novel 4-phenoxypyridine based 3-oxo-3,4-dihydroquinoxaline-2-carboxamide derivatives as potential c-Met kinase inhibitors
Wang, Zhen,Shi, Jiantao,Zhu, Xianglong,Zhao, Wenwen,Gong, Yilin,Hao, Xuechen,Hou, Yunlei,Liu, Yajing,Ding, Shi,Liu, Ju,Chen, Ye
, (2020/10/21)
Blocking c-Met kinase activity by small-molecule inhibitors has been identified as a promising approach for the treatment of cancers. Herein, we described the design, synthesis, and biological evaluation of a series of 4-phenoxypyridine-based 3-oxo-3,4-dihydroquinoxaline derivatives as c-Met kinase inhibitors. Inhibitory activitives against c-Met kinase evaluation indicated that most of compounds showed excellent c-Met kinase activity in vitro, and IC50 values of ten compounds (23a, 23e, 23f, 23l, 23r, 23s, 23v, 23w, 23x and 23y) were less than 10.00 nM. Notably, three of them (23v, 23w and 23y) showed remarkable potency with IC50 values of 2.31 nM, 1.91 nM and 2.44 nM, respectively, and thus they were more potent than positive control drug foretinib (c-Met, IC50 = 2.53 nM). Cytotoxic evaluation indicated the most promising compound 23w showed remarkable cytotoxicity against A549, H460 and HT-29 cell lines with IC50 values of 1.57 μM, 0.94 μM and 0.65 μM, respectively. Furthermore, the acridine orange/ethidium bromide (AO/EB) staining, cell apoptosis assays by flow cytometry, wound-healing assays and transwell migration assays on HT-29 and/or A549 cells of 23w were performed. Especially compound 23w, which displayed potent antitumor, apoptosis induction and antimetastatic activity, could be used as a promising lead for further development. Meanwhile, their preliminary structure-activity relationships (SARs) were also discussed.
Well-Designed N-Heterocyclic Carbene Ligands for Palladium-Catalyzed Denitrative C-N Coupling of Nitroarenes with Amines
Chen, Kai,Chen, Wanzhi,Chen, Wei,Liu, Miaochang,Wu, Huayue
, p. 8110 - 8115 (2019/08/26)
The C-N bond formation is one of the fundamental reactions in organic chemistry, because of the widespread presence of amine moieties in pharmaceuticals and biologically active compounds. Palladium-catalyzed C-N coupling of haloarenes represents one of the most efficient approaches to aromatic amines. Nitroarenes are ideal alternative electrophilic coupling partners, since they are inexpensive and readily available. The denitration and cross-coupling using nitroarenes as the electrophilic partners is challenging, because of the low reactivity of the Ar-NO2 bond toward oxidative addition. We report here the C-N coupling of nitroarenes and amines using palladium/5-(2,4,6-triisopropylphenyl)imidazolylidene[1,5-a]pyridines as the catalyst. The ligands are readily available from commercial chemicals. The reaction shows broad substrate scope and functional group tolerance. The method is applicable to both aromatic and aliphatic amines, and many secondary and tertiary aromatic amines bearing various functional groups were obtained in high yields.
INHIBITING CONNEXIN 46 TO TREAT GLIOBLASTOMA AND OTHER CONDITIONS
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Page/Page column 27; 28, (2019/04/16)
Provided herein are compositions, systems, kits, and methods for treating a disease or condition by administering to a subject an agent that inhibits connexin 46 (Cx46) (e.g., ondancetron, an ondancetron analog or derivative, testosterone, a testosterone
