Khandan Mojtaba, Sadeghian-Rizi Sedighe, Khodarahmi Ghadamali, Hassanzadeh Farshid
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2018 Apr;13(2):168-176. doi: 10.4103/1735-5362.223802.
A series of novel sorafenib analogues containing a quinoxalinedione ring and amide linker were synthesized. A total of 9 novel compounds in 6 synthetic steps were synthesized. Briefly, the amino group of p-aminophenol was first protected which then followed by O-arylation with 5-chloro-2-nitroaniline to provide compound . Reduction of the nitro group of compound and cyclization of the diamine group of compound with oxalic acid afforded compound which on deacetylation yeilded compound . Then compound was reacted with different acyl halides to afford the target compounds . Chemical structures of synthesized compounds were confirmed by 1H NMR and FT-IR analysis. All compounds were evaluated at 1, 10, 50 and 100 μM concentrations for their cytotoxicity against HeLa and MCF-7 cancer cell lines. Some of the compounds showed good cytotoxic activity, especially compounds and with the IC50 values of 19, 16, 22, 18, and 16 μM against MCF-7 cell line and 20, 18, 25, 20, and 18 μM against HeLa cell line, respectively.
合成了一系列含有喹喔啉二酮环和酰胺连接基的新型索拉非尼类似物。通过6步合成总共得到了9种新型化合物。简要来说，对氨基苯酚的氨基首先被保护，然后与5-氯-2-硝基苯胺进行O-芳基化反应得到化合物 。化合物 的硝基还原以及化合物 的二胺基团与草酸环化得到化合物 ，化合物 脱乙酰基得到化合物 。然后化合物 与不同的酰卤反应得到目标化合物 。通过1H NMR和FT-IR分析确认了合成化合物的化学结构。对所有化合物在1、10、50和100 μM浓度下针对HeLa和MCF-7癌细胞系的细胞毒性进行了评估。一些化合物表现出良好的细胞毒性活性，尤其是化合物 和 ，它们对MCF-7细胞系的IC50值分别为19、16、22、18和16 μM，对HeLa细胞系的IC50值分别为20、18、25、20和18 μM。
