- Clofazimine derivatives as potent broad-spectrum antiviral agents with dual-target mechanism
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Thirty-two clofazimine derivatives, of which twenty-two were new, were synthesized and evaluated for their antiviral effects against both rabies virus and pseudo-typed SARS-CoV-2, taking clofazimine (1) as the lead. Among them, compound 15f bearing 4-methoxy-2-pyridyl at the N5-position showed superior or comparable antiviral activities to lead 1, with the EC50 values of 1.45 μM and 14.6 μM and the SI values of 223 and 6.1, respectively. Compound 15f inhibited rabies and SARS-CoV-2 by targeting G or S protein to block membrane fusion, as well as binding to L protein or nsp13 to inhibit intracellular biosynthesis respectively, and thus synergistically exerted a broad-spectrum antiviral effect. The results provided useful scientific data for the development of clofazimine derivatives into a new class of broad-spectrum antiviral candidates.
- Cao, Shouchun,Guo, Zhihao,Huang, Weijin,Li, Yinghong,Li, Yuhua,Liu, Qiang,Liu, Yonghua,Shi, Yulong,Song, Danqing,Wang, Youchun,Wu, Jiajing,Zhang, Xintong,Zhao, Xiaoqiang
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- Clofazimine and intermediate preparation method
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The present invention discloses a 3 - amino - 10 - (4 - chlorophenyl) - 2 (4 - chlorophenyl imine) - 2 - 10 - dihydro phenazino as raw materials for under acidic conditions, in the 30 - 50 °C lower reaction 36 - 96 hours to obtain 2 - amino - 4' - chloro-aniline, its self condensation reaction, to obtain N, 5 - double-(4 - chlorophenyl) - 3 - imino - 3, 5 - dihydro phenazine - 2 - amine, with isopropylamine reaction generating clofazimine. The method of the invention can be recycled in the industrialization process generating a large amount of waste of the 3 - amino - 10 - (4 - chlorophenyl) - 2 (4 - chlorophenyl imine) - 2 - 10 - dihydro phenazine, avoids the waste of the original material, not only can greatly reduce the production cost, also can be the development of the cycle production, in order to save resources and the purpose of environmental protection.
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Paragraph 0026-0028
(2019/02/13)
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