A kind of quinoline carboxamide compound and its preparation method and anti-enterovirus 71 application

A technology of quinoline carboxamide and enterovirus, which is applied in the field of medicine, can solve the problems of stoppage, impossibility of real application, and limited antiviral efficacy, and achieve the effect of low toxicity

Inactive Publication Date: 2021-02-19
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

For example, the viral capsid protein inhibitor pleconaril (Puleconarali), the 3C protease inhibitor rupintrivir (rupintravir), the 3D polymerase inhibitor gemcitabine (gemcitabine) and the PI4KB inhibitor enviroxime (Enwei oxime) have all reached the preclinical level. Or early clinical development stage, but due to limited antiviral efficacy or safety issues, they stop at the clinical research stage and cannot really be applied to the market

Method used

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  • A kind of quinoline carboxamide compound and its preparation method and anti-enterovirus 71 application
  • A kind of quinoline carboxamide compound and its preparation method and anti-enterovirus 71 application
  • A kind of quinoline carboxamide compound and its preparation method and anti-enterovirus 71 application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] [embodiment 1] the preparation of 2-chloroquinoline-4-formyl chloride II-2

[0028] 2-Chloroquinoline-4-formyl chloride is synthesized by the reaction shown in the following formula i.

[0029]

[0030] 2-Chloroquinoline-4-carboxylic acid (100 mg, 0.482 mmol) was added into a 25 mL round bottom flask, and 5 mL of DCM solution and 2 drops of DMF solution were added while stirring. After fully stirring, 0.088 mL of thionyl chloride solution was added dropwise. After the addition was complete, it was heated to 55° C. and refluxed for 4 hours until the reaction solution became clear. Two drops of the reaction solution were placed in an EP tube, and 0.5 mL of methanol solution was added to quench the reaction, and the progress of the reaction was monitored by TLC. After the reaction was completed, spin dry directly for the next step of reaction.

Embodiment 2

[0031] [Example 2] Preparation of 2-chloroquinoline-4-formamide derivatives II-4a-h

[0032] The 2-chloroquinoline-4-carboxamide derivatives II-4a-h are synthesized by the reaction shown in the following formula ii.

[0033]

[0034] Take the preparation of 2-chloro-N-(2-(diethylamino)ethyl)quinoline-4-carboxamide II-4a as an example: N,N-diethylethylenediamine (61.6mg, 0.530 Add mmol) II-3a into a 25 mL round bottom flask, add 5 mL of DCM and triethylamine solution (0.1 mL, 0.646 mmol) under ice-bath conditions, and stir in ice-bath for 15 minutes. Dissolve the spin-dried 2-chloroquinoline-4-formyl chloride (143.8mg, 0.636mmol) in 2mL of DCM in Example 1, add it dropwise to the original reaction solution under ice bath, remove the ice bath after the dropwise addition, and react at room temperature overnight. After the reaction was completed, the reaction solution was spin-dried and separated by column chromatography to obtain 2-chloro-N-(2-(diethylamino)ethyl)quinoline-4...

Embodiment 3

[0036] [Example 3] Preparation of quinoline carboxamide compound II-6-a-q of the present invention

[0037] The quinoline carboxamide compound is synthesized by the reaction shown in the following formula iii.

[0038]

[0039]

[0040] Sodium hydride (21.2mg, 0.883mmol) was added into a 25mL round bottom flask, argon was introduced into the flask under vacuum, and 3mL DMF was added under ice-bath conditions. Dissolve n-butanol (60.6 mg, 0.818 mmol) in 1 mL of DMF and add it to the original reaction solution. After the addition is complete, remove the ice bath and stir at room temperature for 30 minutes. II-4a (100mg, 0.327mmol) and potassium iodide (54.28mg, 0.327mmol) were dissolved in 1mL DMF respectively, and added to the original reaction solution in sequence. After the addition, react at 80°C for 72 hours. The reaction was monitored by TLC. After the reaction was completed, it was quenched with water, extracted with 3×30 mL of ethyl acetate, washed with 10 mL of ...

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PUM

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Abstract

The invention discloses a quinoline formamide compound and a preparation method thereof and an application of an anti-enterovirus type 71 (EV71), and belongs to the technical field of medicine. Specifically, 2-chloroquinoline-4-formamide derivative and an alcohol compound are subjected to a substitution reaction, so that a series of quinoline formamide compounds are prepared. The quinoline formamide compounds have the activity of resisting enterovirus type 71, have small toxicity to cells, can be developed as a new anti-EV 71 drug, and have a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a quinoline carboxamide compound, a preparation method thereof and an anti-enterovirus 71 application. Background technique [0002] Human enterovirus 71 (EV71) is a non-enveloped, single-stranded RNA virus belonging to the Picornaviridae family. The EV71 virus can be divided into three genotypes (A, B, C), which can be subdivided into eleven subtypes according to the sequence of the structural protein VP1. Genotype A contains only the original strain (BrCr), while genotype B and genotype C each contain five subtypes (B1-B5, C1-C5). Currently, the subtype of EV71 prevalent in my country is mainly the C4 genotype. [0003] EV71, first isolated from the feces of infants with encephalitis in 1969, is the main causative agent of hand, foot and mouth disease (HFMD), which mainly occurs in young children, causing fever and rashes on hands, feet, mouth and other parts , herpes as the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/50A61P31/14A61K31/4709A61K31/47
CPCA61P31/14C07D215/50
Inventor 吴叔文周海兵蓝柯许智超
Owner WUHAN UNIV
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