38699-66-0Relevant academic research and scientific papers
Discovery and optimization of new 6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline derivatives as potent influenza virus PAN inhibitors
Liu, Zhihao,Gu, Shuyin,Zhu, Xiang,Liu, Mingjian,Cao, Zhenqing,Qiu, Pengsen,Li, Sumei,Liu, Shuwen,Song, Gaopeng
, (2021/10/27)
Annual unpredictable efficacy of vaccines, coupled with emerging drug resistance, underlines the development of new antiviral drugs to treat influenza infections. The N-terminal domain of the PA (PAN) endonuclease is both highly conserved across influenza strains and serotypes and is indispensable for the viral lifecycle, making it an attractive target for new antiviral therapies. Here, we describe the discovery of a new class of PAN inhibitors derived from recently identified, highly active hits for PAN endonuclease inhibition. By use of structure-guided design and systematic SAR exploration, the hits were elaborated through a fragment growing strategy, giving rise to a series of 1, 3-cis-2-substituted-1-(3, 4-dihydroxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid derivatives as potent PAN inhibitors. This approach ultimately resulted in the development of a new lead compound 13e, which exhibited an EC50 value of 4.50 μM against H1N1 influenza virus in MDCK cells.
Polyphenol compound containing tetrahydropapaverine-3-methyl carboxylate, preparation method and applications thereof
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, (2020/02/14)
The invention discloses a polyphenol compound containing tetrahydropapaverine-3-methyl carboxylate, a preparation method and applications thereof, wherein the polyphenol compound has a structure represented by a formula I, and R is hydrogen, halogen, C1-8 alkyl, C1-8 cycloalkyl, C1-8 halogenated alkyl, C1-8 alkoxy, C1-8 halogenated alkoxy, C2-4 alkenyl, phenyl, halogenated phenyl, nitrophenyl, C1-4 alkyl substituted phenyl, C1-4 halogenated alkyl substituted phenyl, naphthalene or acylamino. According to the invention, the polyphenol compound is novel in structure and generally has relativelygood inhibitory activity on influenza A virus H1N1, and the inhibitory effect of most compounds is superior to the inhibitory effect of a positive control Perimivir, so that the results show that thecompound has obvious inhibiting effect on influenza A virus, can be prepared into anti-influenza A virus medicine to be applied, has good application prospects in prevention and treatment of influenzavirus infection, and expands the application of tetrahydropapaverine structures as anti-influenza virus medicine.
