tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2019 Aug 6:126605. doi: 10.1016/j.bmcl.2019.08.009. [Epub ahead of print]
[h=1]Novel amides modified rupestonic acid derivatives as anti-influenza virus reagents.[/h] Li G[SUP]1[/SUP], Obul M[SUP]2[/SUP], Zhao JY[SUP]1[/SUP], Liu GY[SUP]1[/SUP], Lu W[SUP]3[/SUP], Aisa HA[SUP]4[/SUP].
[h=3]Author information[/h] 1 Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China. 2 Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China; University of Chinese Academy of Sciences, Yuquan Rd 19 A, Beijing 100049, PR China. 3 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China. Electronic address: wlu@chem.ecnu.edu.cn. 4 Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China. Electronic address: haji@ms.xjb.ac.cn.
[h=3]Abstract[/h] In spired by the important role of amide groups of anti-influenza drugs oseltamivir, zanamivir and peramivir in bioactivity, a series of novel amides modified rupestonic acid derivatives were designed and synthesized. The absolute configuration of critical intermediate bearing chloride with newly formed stereocenter was confirmed by X-ray crystallographic analysis. And all new compounds were evaluated for their in vitro inhibitory activities against influenza A (H1N1 and H3N2) and influenza B viruses. The bioassay results showed that 5h with 4-fluorbenzylsulfonyl modified to 2 position of methyl rupestonate displayed the highest activity against influenza A (H1N1 and H3N2) viruses, even stronger than reference drugs oseltamivir and ribavirin (RVB), and might be recommended as a lead compound to further develop the new anti-influenza reagent.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Amide; Anti-influenza virus; Rupestonic acid; X-ray crystallographic analysis
PMID: 31439378 DOI: 10.1016/j.bmcl.2019.08.009
[h=1]Novel amides modified rupestonic acid derivatives as anti-influenza virus reagents.[/h] Li G[SUP]1[/SUP], Obul M[SUP]2[/SUP], Zhao JY[SUP]1[/SUP], Liu GY[SUP]1[/SUP], Lu W[SUP]3[/SUP], Aisa HA[SUP]4[/SUP].
[h=3]Author information[/h] 1 Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China. 2 Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China; University of Chinese Academy of Sciences, Yuquan Rd 19 A, Beijing 100049, PR China. 3 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China. Electronic address: wlu@chem.ecnu.edu.cn. 4 Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China. Electronic address: haji@ms.xjb.ac.cn.
[h=3]Abstract[/h] In spired by the important role of amide groups of anti-influenza drugs oseltamivir, zanamivir and peramivir in bioactivity, a series of novel amides modified rupestonic acid derivatives were designed and synthesized. The absolute configuration of critical intermediate bearing chloride with newly formed stereocenter was confirmed by X-ray crystallographic analysis. And all new compounds were evaluated for their in vitro inhibitory activities against influenza A (H1N1 and H3N2) and influenza B viruses. The bioassay results showed that 5h with 4-fluorbenzylsulfonyl modified to 2 position of methyl rupestonate displayed the highest activity against influenza A (H1N1 and H3N2) viruses, even stronger than reference drugs oseltamivir and ribavirin (RVB), and might be recommended as a lead compound to further develop the new anti-influenza reagent.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Amide; Anti-influenza virus; Rupestonic acid; X-ray crystallographic analysis
PMID: 31439378 DOI: 10.1016/j.bmcl.2019.08.009