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Coumarin/pyridine hybrid derivative as well as preparation method and application thereof

A technology of coumarin and pyridone, which can be used in drug combinations, nervous system diseases, organic chemistry, etc., can solve the problems of low specificity, complex pathogenesis of Alzheimer's disease, and single therapeutic effect.

Active Publication Date: 2019-04-26
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the complex pathogenesis of Alzheimer's disease, the above drugs can only alleviate or inhibit the disease, but cannot completely cure it
Since the therapeutic effect of drugs targeting a single target is single and the pertinence is not high, more and more researches are biased towards the development of dual-target or multi-target drugs, targeting multiple targets of disease occurrence, which may make it The curative effect is enhanced, making up for the shortcoming of a single drug with a single effect, and improving the therapeutic effect

Method used

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  • Coumarin/pyridine hybrid derivative as well as preparation method and application thereof
  • Coumarin/pyridine hybrid derivative as well as preparation method and application thereof
  • Coumarin/pyridine hybrid derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] 2-Methyl-3-hydroxy-1-(2-(4-(((coumarin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl ) ethyl) the preparation method of pyridin-4-ketone (Ia)

[0104]

[0105] 7-(prop-2-yn-1-yloxy)-coumarin (1.2mmol), 1-(2-azidoethyl)-3-methoxy-2-methyl-4-one (1mmol), CuSO 4 ·5H 2 O (0.1 mmol), L-sodium ascorbate (0.5 mmol), MeOH (5 mL), H 2 O (5 mL), control the reaction temperature at 25°C, and react for 24h. The reaction was monitored by TLC. After the conversion of the raw materials was complete, the reaction was stopped, concentrated, and purified by silica gel column chromatography (dichloromethane:methanol=20:1 as eluent) to obtain a white solid intermediate.

[0106] Add the above-mentioned white intermediate (0.84mmol) and anhydrous dichloromethane (10mL) into a single-necked flask, and dissolve boron tribromide (3.6mmol) in anhydrous dichloromethane (10mL) and place in a constant pressure dropping funnel, N 2 Under protection, boron tribromide was slowly added dropwise at 0...

Embodiment 2

[0111] 2-Methyl-3-hydroxy-1-(3-(4-(((coumarin-7-yl)oxy)methyl)-1,2,3-triazol-1-yl)propane Base) the preparation method of pyridin-4-ketone (Ib)

[0112]

[0113] 7-(prop-2-yn-1-yloxy)-coumarin (1.2mmol), 1-(3-azidopropyl)-3-methoxy-2-methylpyridine-4- Ketone (1 mmol), CuSO 4 ·5H 2 O (0.1 mmol), L-sodium ascorbate (0.5 mmol), MeOH (5 mL), H 2 O (5 mL), control the reaction temperature at 25°C, and react for 24h. The reaction was monitored by TLC. After the conversion of the raw materials was complete, the reaction was stopped, concentrated, and purified by silica gel column chromatography (dichloromethane:methanol=20:1 as eluent) to obtain a white solid intermediate.

[0114] Add the above-mentioned white intermediate (0.82mmol) and anhydrous dichloromethane (10mL) into a single-necked flask, and dissolve boron tribromide (2.4mmol) in anhydrous dichloromethane (10mL) and place in a constant pressure dropping funnel, N 2 Under protection, boron tribromide was slowly add...

Embodiment 3

[0119] 2-(Hydroxymethyl)-3-hydroxy-6-methyl-1-(2-(4-(((coumarin-7-yl)oxy)methyl)-1,2,3-tri The preparation method of oxazol-1-yl) ethyl) pyridin-4-one (Ic)

[0120]

[0121] 7-(prop-2-yn-1-yloxy)-coumarin (1.2mmol), 1-(2-azidoethyl)-2-(hydroxymethyl)-3-methoxy- 6-Methylpyridin-4-one (1mmol), CuSO 4 ·5H 2 O (0.1 mmol), L-sodium ascorbate (0.5 mmol), MeOH (5 mL), H 2 O (5 mL), control the reaction temperature at 25°C, and react for 24h. The reaction was monitored by TLC. After the conversion of the raw materials was complete, the reaction was stopped, concentrated, and purified by silica gel column chromatography (dichloromethane:methanol=20:1 as eluent) to obtain a white solid intermediate.

[0122] Add the above-mentioned white intermediate (0.80mmol) and anhydrous dichloromethane (10mL) into a single-necked flask, and dissolve boron tribromide (2.4mmol) in anhydrous dichloromethane (10mL) and place in a constant pressure dropping funnel, N 2 Under protection, boron t...

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Abstract

The invention provides a coumarin / pyridine hybrid derivative shown as the formula (I) or the formula (II) and pharmaceutically acceptable salt thereof. The coumarin / pyridine hybrid derivative and thepharmaceutically acceptable salt thereof can be applied in preparation of anti-Alzheimer and antiparkinsonian drugs or drugs for treating other diseases by inhibiting MAOs (monoamine oxidases) or chelating iron ions.

Description

technical field [0001] The invention relates to the fields of organic synthesis and medicinal chemistry, in particular to a class of dual-target anti-Alzheimer's coumarin / pyridone hybrid derivatives with monoamine oxidase inhibitory effect and iron ion chelating ability and preparation thereof Methods and uses in the treatment of Alzheimer's disease. Background technique [0002] Alzheimer's disease (Alzheimer's disease, AD) is the most common degenerative disease of the central nervous system in middle-aged and elderly people, mainly manifested by cognitive and behavioral dysfunction. With the increase of global aging and the increasing pollution of the environment, Worldwide, this disease has become a serious disease that threatens human health after cardiovascular disease and tumors, especially in China. Because Alzheimer's disease can cause patients to be unable to take care of themselves, it has caused serious harm to human health and social stability. In recent years...

Claims

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Application Information

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IPC IPC(8): C07D405/14A61P25/28
CPCA61P25/28C07D405/14
Inventor 谢媛媛蒋筱莹甘兵米治胜白仁仁林玉燕姚传胜
Owner ZHEJIANG UNIV OF TECH
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