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Chrysin amide derivative as well as preparation method and medical application thereof

A technology of coyne amide and its derivatives, applied in the field of coyne amide derivatives and their preparation, can solve the problems that there are no research reports on uric acid-lowering and anti-gout of coyne amide derivatives, and achieve the effect of good water solubility

Pending Publication Date: 2019-05-17
武汉翼博济生生物科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Although it has been reported in the literature that coine has the effects of lowering uric acid and anti-inflammation, there is no research report on the effect of coinamide derivatives on lowering uric acid and anti-gout

Method used

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  • Chrysin amide derivative as well as preparation method and medical application thereof
  • Chrysin amide derivative as well as preparation method and medical application thereof
  • Chrysin amide derivative as well as preparation method and medical application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: Preparation of coyne amide derivatives

[0028] 1. Add coyne and anhydrous potassium carbonate to an appropriate amount of acetone and stir, then add ethyl bromoacetate to the solution, and heat and reflux under the condition of stirring while heating; wherein coyne, anhydrous potassium carbonate , The molar ratio of ethyl bromoacetate is 1:(1~2):(1~2). After the reaction was over, it was cooled. Suction filter the solution, concentrate the filtrate to a density of 1.1-1.3 after suction filtration, wash the filtrate concentrate with petroleum ether, 1wt% NaOH solution and pure water successively, then vacuum-dry and purify through a silica gel column.

[0029]

[0030] 2. Dissolve the product obtained in step 1 in an appropriate amount of methanol, add KOH to the solution and reflux under heating and stirring to dissolve; wherein the molar ratio of KOH to coine is (0.2-0.5):1. Suction filtration, the filtered solid was washed with methanol and dried. ...

Embodiment 2

[0035] Example 2: Pharmacological Activity Screening of Coinamide Derivatives

[0036] 1. Screening for inhibition of xanthine oxidase activity

[0037] The biochemical basis of hyperuricemia and gout is excessive uric acid concentration in body fluids, and reducing excessive uric acid is the main treatment strategy. Xanthine oxidase (Xanthine oxidase, XO) is a key enzyme in the production of uric acid, which catalyzes the production of uric acid from hypoxanthine and xanthine, and at the same time produces a large amount of active oxygen such as superoxide anion and hydrogen peroxide. Therefore, XO is a good high Targets for treatment of uric acidemia and gout.

[0038] 1.1 Preparation of reagents

[0039] 1.1.1 Preparation of test solution

[0040] (1) Preparation of dipotassium hydrogen phosphate buffer solution (pH=7.5, 50mM, prepared according to the appendix of "Pharmacopoeia of the People's Republic of China" 2010 edition): that is, accurately weigh the anhydrous hyd...

Embodiment 3

[0064] Embodiment 3: oil-water partition coefficient

[0065] The oil-water partition coefficient of each compound was determined by the classic n-octanol-water system, wherein the oil-water partition coefficient IgP of coyne was 4.52, and the oil-water partition coefficient IgP of other coyne amide derivatives is shown in the sixth column of Table 1. It can be seen from the table that the oil-water partition coefficients of coyne amide derivatives prepared in Example 1 are better than those of coyne, indicating that they have better water solubility and better druggability.

[0066] Table 1. IC50 values ​​and IgP of coyne series derivatives inhibiting xanthine oxidase, TNF-α and IL-1β

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[0078]

[0079] Conclusion: The coyne amide derivatives proposed in the present invention have good water solubility, stability and pharmacological activity ch...

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Abstract

The invention relates to the technical field of pharmaceutical chemistry and in particular relates to a chrysin amide derivative as well as a preparation method and medical application of the derivative. A structural formula of the chrysin amide derivative provided by the invention is shown as a formula I; a substituent group R in the compound is a series of acylamino. The chrysin amide derivativeprovided by the invention has the characteristics of good water solubility, stability and pharmacological activity; the preparation method of each chrysin amide derivative is the same and comprises the following steps: connecting 7th-site hydroxyl of chrysin with ethyl bromoacetate and then hydrolyzing; finally, carrying out amide condensation reaction on a series of amide compounds respectively,so as to obtain a series of chrysin amide derivatives. A pharmacodynamic screening experiment result shows that compared with the chrysin, the compound has better water solubility and better uric acid lowering and gout and inflammation resisting effects and is a compound which has a prospect of being developed into a novel anti-gout drug.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a coyne amide derivative, a preparation method thereof and a medical application thereof. Background technique [0002] Coin, also known as chrysin, is a flavonoid natural product with various activities. Modern studies have shown that it has various pharmacological activities such as anti-tumor, anti-inflammation, anti-oxidation, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, due to its own structure , water solubility and other reasons make its pharmacological activity low, which greatly affects the bioavailability of coine. The only dosage form used in clinical trials is emulsion, which has poor stability; intravenous administration has obvious vascular irritation, and it is difficult to reach the site of action, which limits its clinical application. Therefore, it is necessary to modify and improve its structure in order to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/30C07D417/12C07D471/04C07D405/12C07F9/655A61K31/352A61K31/428A61K31/437A61K31/4433A61K31/55A61K31/4025A61K31/4045A61K31/665A61P19/06
Inventor 马菊娥
Owner 武汉翼博济生生物科技有限公司
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