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Antiviral drug Musellarin and analogue molecule, preparation method and application

A technology of antiviral drugs and analogs, applied in antiviral agents, organic chemistry, etc., can solve the problems of limited types of influenza virus drugs and large side effects, and achieve low cytotoxicity, low cost, and strong inhibitory effect

Active Publication Date: 2021-01-15
HKUST SHENZHEN RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The purpose of the present invention is to overcome the above-mentioned deficiencies of the prior art, to provide a kind of antiviral drug Musellarin and its analog molecule with influenza A virus RNA polymerase as the target and its preparation method and application, aiming to solve the problem of existing influenza virus Limited types of drugs, technical problems with large side effects

Method used

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  • Antiviral drug Musellarin and analogue molecule, preparation method and application
  • Antiviral drug Musellarin and analogue molecule, preparation method and application
  • Antiviral drug Musellarin and analogue molecule, preparation method and application

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preparation example Construction

[0038] On the other hand, the embodiment of the present invention also provides a kind of antiviral drug Musellarin and the preparation method of analog molecule with influenza A virus RNA polymerase as the target, comprising the following steps:

[0039] S01: the furfuryl alcohol substrate shown in formula 4 is carried out Achmatowicz rearrangement reaction, then carries out acetylation reaction, obtains the compound shown in formula 5;

[0040] S02: deoxidizing the compound shown in formula 5 to obtain the compound shown in formula 6;

[0041] S03: The compound shown in formula 6 is carried out coupling reaction with the diazonium salt shown in formula 7-9 respectively, obtains the compound shown in formula 10-12 respectively;

[0042] S04: the compound shown in formula 10-12 is successively subjected to reduction reaction, intramolecular Friedel-Crafts ring-closure reaction and deprotection reaction;

[0043]

[0044] The embodiment of the present invention provides a m...

Embodiment 1

[0067] The preparation of compound shown in embodiment 1 formula 1-formula 3

[0068] (1) a kind of antiviral drug Musellarin and analog molecule with influenza A virus RNA polymerase as target, molecular structure is as shown in formula 1, and its preparation method comprises the following steps:

[0069] Provide 4.01g of furfuryl alcohol compound shown in Formula 4, 20ml of tetrahydrofuran / 5ml of water as the reaction medium, add 3.65g of potassium persulfate preparation, 118mg of potassium bromide and 416mg of sodium bicarbonate at 0°C, and react 1-2 at 0°C Hours, quench the reaction with sodium bicarbonate, extract and concentrate to obtain the crude product, then add the crude product to 20ml of DCM, add acetic anhydride 1.52g and triethylammonia 2.02 at 0°C, and react at 0°C for 4 hours, The reaction was quenched with aqueous ammonium chloride solution, extracted and concentrated to obtain a crude product, which was separated by column chromatography to obtain 4.1 g of d...

Embodiment 2

[0080] Embodiment 2 semi-lethal concentration (LC50) experiment

[0081] Prepare required culture media and solutions: Prepare Mirus - LT1 transfection agent and medium consisting of 5% FBS and 1% P / S Opti-MEM medium. Prepare and culture HEK-293T cells. Prepare 0.2 μg of DNA solution per well in a 96-well plate.

[0082] Cell culture: at T-75cm 2 HEK-293T cells were cultured in flasks until the cell density reached 70%-80%, and were continuously passaged for 3 times. Cells were collected 24 hours before the experiment, and each 96-well plate was inoculated with approximately 2×10 6 cells and incubate the cells overnight.

[0083] Generating transfection complex: prepare 1.43mL serum-free medium, transfect and add 22μg DNA plasmid, add 66μl TransIT-1L, mix well. Incubate at room temperature for 15-30 minutes to form transfection complexes, and add 13 μL of master mix to each well of a 96-well plate.

[0084] Trypsinize the cells in the standard medium, add an appropriat...

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Abstract

The invention belongs to the technical field of medicinal chemistry, and particularly relates to an antiviral drug Musellarin and analogue molecule taking influenza A virus RNA polymerase as a target,a preparation method and application. The chemical structural general formula of the molecule is shown as a formula i in the specification, in the formula i, R1 is selected from hydroxyl or alkoxy, R2 is selected from hydroxyl or alkoxy, R3 is selected from hydrogen atom, hydroxyl or alkoxy, and R4 is selected from hydroxyl or alkoxy. According to the antiviral drug Musellarin and analogue molecule provided by the invention, the influenza virus RNA polymerase is taken as a target, the transcription and replication processes of influenza virus are directly blocked by inhibiting the activity ofthe influenza virus RNA polymerase, and the molecule has efficient inhibition property and high selectivity by taking the influenza virus RNA polymerase as the target, so that the molecule has the potential of being developed into an anti-influenza virus drug molecule.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to an antiviral drug Musellarin and an analog molecule, a preparation method and an application of the influenza A virus RNA polymerase as a target. Background technique [0002] Avian influenza is a kind of infectious disease caused by infection of avian influenza virus, which has many subtypes and is highly prone to mutation. Currently common avian influenza virus subtypes mainly include H5N1, H1N1, H5N2, H7N3, H7N7, H9N2 and H7N9 subtypes. Among them, the H7N9 virus is a newly discovered influenza subtype. Its fatality rate of up to 40% has attracted worldwide attention, and researchers have begun to actively study drugs for this type of disease. [0003] The currently reported anti-influenza drugs can be divided into four categories according to their targets. The first category is amantadine and ethylamine, which can inhibit the M2 protein of the viru...

Claims

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Application Information

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IPC IPC(8): C07D311/92A61P31/16
CPCC07D311/92A61P31/16
Inventor 黄旭辉张栢恒童荣标许新洲李志龙郑伟锋
Owner HKUST SHENZHEN RES INST
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