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Copper‐Catalyzed Multicomponent Reaction to Construct Fluorinated Indole‐quinoxalin‐2(1<i>H</i>)‐ones and Their Biological Evaluation

Letian Zhang, Yong Yang, Pengfei Zhang, Chao Chen, Chao Shen

2022European Journal of Organic Chemistry12 citationsDOI

Abstract

Abstract A practical and mild three‐component reaction of indoles, quinoxalin‐2(1 H )‐ones, and CF 3 SO 2 Na is disclosed for the facile access of various 3‐[2‐(trifluoromethyl)1 H ‐indol‐3‐yl]quinoxalin‐2(1 H )‐ones using low‐cost and catalytic amount of CuF 2 as the catalyst. This strategy exhibits high site‐selectivity, step economy, and broad substrates scope. Synthetic utility was demonstrated by the one‐pot two‐step synthesis of N ‐alkyl triazoles compounds via a click chemistry. To evaluate the antiproliferative activity of these compounds, A549 s (human lung adenocarcinoma cells) and HUVECs, as a model of toxicity, were used in MTT assay. The outcomes disclosed for 6‐CO 2 Me and a N ‐alkyl triazole derivatives were of potent antiproliferative effect against A549 s (IC 50 = 4.7 and 14.9 μM, respectively) with slight cytotoxicity in HUVECs. Morphological study was conducted by AO/EB dual staining, indicated hydrochloride 6‐CO 2 Me derivative was capable of inducing apoptosis of A549 cells.

Topics & Concepts

ChemistryCytotoxicityA549 cellCatalysisSelectivityHydrochlorideCombinatorial chemistryMTT assayIndole testTrifluoromethylStereochemistryAlkylMedicinal chemistryIn vitroOrganic chemistryBiochemistrySynthesis and Biological EvaluationFluorine in Organic ChemistryClick Chemistry and Applications
Copper‐Catalyzed Multicomponent Reaction to Construct Fluorinated Indole‐quinoxalin‐2(1<i>H</i>)‐ones and Their Biological Evaluation | Litcius