- Design, Synthesis and Biological Evaluation of Novel α-Acyloxycarboxamide-Based Derivatives as c-Met Inhibitors
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Dysregulated HGF/c-Met signalling has been associated with many human cancers, poor clinical outcomes, and even resistance acquisition to some approved targeted therapies. As such, c-Met kinase has emerged as an attractive target for anticancer drug discovery. Herein, a series of 6,7-disubstitued-4-(2-fluorophenoxy)quinoline derivatives bearing α-acyloxycarboxamide moiety were designed, synthesized via Passerini reaction as the key step, and evaluated for their in vitro biological activities against c-Met kinase and five selected cancer cell lines. The preliminary structure-activity relationship demonstrated that α-acyloxycarboxamide as the 5-atom linker maintained the potent antitumor potency. Among these compounds, compound 25s (c-Met IC50 = 4.06 nmol/L) was identified as the most promising lead compound and displayed the most potent antiproliferative activities against A549, HT-29 and MDA-MB-231 cell lines with IC50 of 0.39, 0.20, and 0.58 μmol/L, which were 1.3-, 1.4- and 1.2-fold superior to foretinib, respectively. The further studies indicated that compound 25s can induce apoptosis of A549 cells and arrest efficiently the cell cycle distribution in G2/M phase of A549 cells. Moreover, compound 25s can also inhibit c-Met phosphorylation in A549 cells by a dose-dependent manner. Collectively, these results indicated that compound 25s could be a potential anticancer lead compound deserving for further development.
- Feng, Yu-juan,Ren, Yu-Lin,Zhao, Li-Ming,Xue, Guo-Qiang,Yu, Wen-Hao,Yang, Jia-Qi,Liu, Jun-Wei
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p. 2241 - 2250
(2021/06/28)
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- Formation of new C-O and C-N bonds via base promoted Csp2-Csp3 bond cleavage of α-nitro ketone
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A catalyst free protocol has been developed for nucleophilic Csp2-Csp3 bond cleavage of α-nitroketone in the presence of potassium carbonate to create new C-O and C-N bonds. A series of different substituted α-nitroketones could be selectively cleaved and converted into corresponding esters and tosylamides in the presence of alcohols and bromamine-T, respectively.
- Sarma, Manas Jyoti,Borah, Arun Jyoti,Rajbongshi, Kamal Krishna,Phukan, Prodeep
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supporting information
p. 7008 - 7011
(2015/11/27)
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- Palladium-catalysed carbonylative α-arylation of nitromethane
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A simple and mild Pd-catalysed carbonylative α-arylation of nitromethane has been realised providing access to α-nitro aryl ketones from an array of aryl and heteroaryl iodides. The methodology requires only a mild base and uses the convenient solid CO re
- Lian, Zhong,Friis, Stig D.,Skrydstrup, Troels
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supporting information
p. 3600 - 3603
(2015/04/13)
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- Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization
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A mild, efficient and versatile method has been developed for the construction of a functionalized natural product, meridianin, and its post conversion to pyrimido-β-carboline by cationic π-cyclization. The strategy involves the introduction of an amino g
- Agarwal, Piyush K.,Dathi, Meena D.,Saifuddin, Mohammad,Kundu, Bijoy
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supporting information
p. 1901 - 1908
(2013/01/16)
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- A New Method for the Preparation of α-Nitroacetophenones
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Treatment of readily available substituted β-nitrostyrenes with tert-butyl hydroperoxide and butyllithium gives synthetically useful α-nitroacetophenones in good yield.
- Ashwell, Mark A.,Jackson, Richard F. W.
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p. 229 - 231
(2007/10/02)
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