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Aminothiazole compound as well as preparation method and application thereof in resisting enterovirus 71

A technology of aminothiazole and enterovirus, which is applied in the field of medicine to achieve the effect of low toxicity

Inactive Publication Date: 2019-12-20
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is still a lack of drugs that can effectively treat HFMD. Clinica

Method used

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  • Aminothiazole compound as well as preparation method and application thereof in resisting enterovirus 71
  • Aminothiazole compound as well as preparation method and application thereof in resisting enterovirus 71
  • Aminothiazole compound as well as preparation method and application thereof in resisting enterovirus 71

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] [Example 1] Preparation of aromatic heterocyclic thiourea derivatives with substituent R

[0030] The aromatic heterocyclic thiourea derivatives with R are synthesized by the reaction shown in the following formula i.

[0031]

[0032] Taking the preparation of 1-(2,6-dibromophenyl)thiourea 2m as an example, the steps are as follows: Dissolve ammonium thiocyanate (273.0mg, 3.6mmol) in 15mL of acetone, then add benzoyl chloride (460.2mg , 3.38mmol), reflux for 15min. Cool to room temperature, add 2,6-dibromoaniline 1m (600mg, 2.4mmol), and reflux for 30min. After cooling to room temperature, pour into ice water and stir for 30 min. Let stand for two minutes, filter with a suction filter, wash the precipitate with water, dissolve the solid in 15mL of 10% NaOH solution after drying, heat and stir at 80°C for 30min, cool to room temperature, slowly add 6N hydrochloric acid dropwise until the pH of the solution is 1- 2. Stir for 30 minutes, then adjust the pH to 10 wit...

Embodiment 2

[0034] [Example 2] with R 2 Preparation of α-Chloroacetone Derivatives

[0035] Synthesized by the reactions shown in the following formulas ii and iii to obtain with R 2 α-chloroacetone derivatives.

[0036]

[0037] Taking the preparation of 2-chloro-1-(imidazo[1,2-a]pyrimidin-3-yl)ethan-1-one 5a as an example, the steps are as follows: Weigh 2-aminopyrimidine 3a (1g, 10.5mmol) Dissolve in 20mL of toluene, add N,N-dimethyl dimethyl acetal (1.38g, 11.6mmol), and reflux for 6h. After the completion of the reaction was monitored by TLC spotting, the reaction was spin-dried to obtain the crude product N,N-dimethyl-N'-(pyrimidin-2-yl)formamidine 4a. Dissolve it in 15 mL of dichloromethane, add 1,3-dichloroacetone (2 g, 15.8 mmol), and reflux overnight. After the completion of the reaction was monitored by TLC, it was concentrated and purified through a silica gel column with a mobile phase ratio of petroleum ether and ethyl acetate (V / V=1 / 3). Finally, 700 mg of 2-chloro-1...

Embodiment 3

[0040] [Example 3] Preparation of aminothiazole compounds of the present invention

[0041] Aminothiazole compounds are synthesized through reactions shown in the following formulas iv and v.

[0042] Take 1.0 equivalent of the aromatic heterocyclic thiourea derivative prepared in Example 1 and place it in a 25 mL single-necked bottle, add 8 mL of absolute ethanol, then add 1.0 equivalent of the compound prepared or purchased in Example 2, and reflux overnight. The reaction was monitored by TLC, and after confirming that the reaction was complete, aminothiazole compounds were obtained by separation and purification by silica gel column chromatography. The reaction formula is as follows:

[0043]

[0044] R 1 for

[0045] R 2 for 6a-6x above correspond to I-1 to I-24 in Table 1.

[0046](1) Preparation of N-(2-bromophenyl)-4-(imidazo[1,2-a]pyrimidin-3-yl)thiazol-2-amine (I-1) Compound 2a N-(2 The preparation of -bromophenyl)-4-(imidazo[1,2-a]pyrimidin-3-yl)thiazo...

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PUM

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Abstract

The invention discloses an aminothiazole compound as well as a preparation method and application thereof in resisting enterovirus 71. The invention belongs to the technical field of medicines. Specifically, 2-chloro-1-(imidazo[1,2-a]pyrimidin-3-yl)ethan-1-one, 2-chloro-1-(imidazo[1,2-a]pyrimidin-3-yl)ethan-1-one or alpha-bromoacetophenone compounds and aromatic heterocyclic thiourea derivatives are used as raw materials, and a series of aminothiazole compounds are prepared through a cyclization reaction. The aminothiazole compound has the activity of resisting enterovirus 71, has low toxicityto cells, can be developed as a new anti-EV71 drug, and has a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to an aminothiazole compound, a preparation method thereof and an anti-enterovirus 71 application. Background technique [0002] Enteroviruses are non-enveloped single-stranded RNA viruses of the picornaviridae family with high mutation rates. Enteroviruses include human enteroviruses (A, B, C, D) and non-human enteroviruses, while EV71 belongs to human enteroviruses. 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). [0003] HFMD, which poses a serious threat to the life and health of infants, is mainly caused by EV71 and CA16. HFMD can cause an acute infectious disease characterized by fever, rashes on the hands, feet, and mouth, herpes, and...

Claims

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Application Information

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IPC IPC(8): C07D487/04C07D277/42A61P31/14
CPCA61P31/14C07D277/42C07D487/04
Inventor 吴叔文周海兵蓝柯许智超
Owner WUHAN UNIV
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