Department of Chemistry and Physics, Augusta University, Augusta, GA 30912, USA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Department of Chemistry and Physics, Augusta University, Augusta, GA 30912, USA.
Bioorg Chem. 2021 Sep;114:105117. doi: 10.1016/j.bioorg.2021.105117. Epub 2021 Jun 23.
At present therapeutic options for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are very limited. We designed and synthesized three sets of small molecules using quinoline scaffolds. A series of quinoline conjugates (10a-l, 11a-c, and 12a-e) by incorporating 1,2,3-triazole were synthesized via a modified microwave-assisted click chemistry technique. Among the synthesized conjugates, 4-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-fluoro-2-(trifluoromethyl)quinoline (10g) and 6-fluoro-4-(2-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)ethoxy)-2-(trifluoromethyl)quinoline (12c) show high potency against SARS-CoV-2. The selectivity index (SI) of compounds 10g and 12c also indicates the significant efficacy compared to the reference drugs.
目前，治疗严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）的方法非常有限。我们使用喹啉支架设计并合成了三组小分子。通过改良的微波辅助点击化学技术，合成了一系列含有 1,2,3-三唑的喹啉缀合物（10a-l、11a-c 和 12a-e）。在合成的缀合物中，4-((1-(2-氯苯基)-1H-1,2,3-三唑-4-基)甲氧基)-6-氟-2-(三氟甲基)喹啉（10g）和 6-氟-4-(2-(1-(4-甲氧基苯基)-1H-1,2,3-三唑-4-基)乙氧基)-2-(三氟甲基)喹啉（12c）对 SARS-CoV-2 表现出高活性。化合物 10g 和 12c 的选择性指数（SI）也表明与参比药物相比，它们具有显著的疗效。
