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2-Substituted-18β-glycyrrhetinic acid derivatives and their applications

A technology of glycyrrhetic acid and compound, applied in the field of medicine, can solve the problems of weak anti-cancer activity, poor physical and chemical properties, difficult to achieve clinical use, etc.

Active Publication Date: 2021-11-05
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although 18β-glycyrrhetinic acid has the above-mentioned excellent properties, its anticancer activity is not strong and its physical and chemical properties are not good, so it is difficult to achieve clinical use

Method used

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  • 2-Substituted-18β-glycyrrhetinic acid derivatives and their applications
  • 2-Substituted-18β-glycyrrhetinic acid derivatives and their applications
  • 2-Substituted-18β-glycyrrhetinic acid derivatives and their applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0156] Example 1: (E)-2-((3,11-dioxo-18β-oleanane-12-ene-30-carboxylate benzyl ester)-2(1H)-ethylidene)-carboxy acid preparation

[0157] Step A: Preparation of 3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid

[0158]

[0159] Take 5g of 18β-glycyrrhetinic acid (10.6mmol) in a 1L eggplant-shaped bottle, then add 500mL of acetone to dissolve, add 6mL of Jones reagent dropwise at 0°C, stir and react at 0°C for 1.5h, then distill out about half acetone, pour the reaction solution into cold water to precipitate a solid, stir for 15 min, filter with suction, and dry to obtain a white solid. Yield: 96.25%, LC-MS: 491.4[M+Na] + ,467.1[M-H] - .

[0160] Step B: Preparation of benzyl 3,11-dioxo-18β-oleanane-12-ene-30-carboxylate

[0161]

[0162] Take 5g (10.6mmol) of 3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid and place it in a 250mL eggplant-shaped bottle, add 4.39g (31.8mmol) of anhydrous potassium carbonate, and then Add 80 mL of dry N,N-dimethylformamide to dis...

Embodiment 2

[0166] Example 2: (E)-2-((3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid methyl ester)-2(1H)-ethylidene)-carboxy acid preparation

[0167] Step A: Preparation of methyl 3β-hydroxy-11-oxo-18β-oleanane-12-ene-30-carboxylate

[0168]

[0169] Take 5g of 18β-glycyrrhetinic acid (10.6mmol) in a 500mL eggplant-shaped bottle, add 250mL of anhydrous methanol to dissolve, cool at 0°C for 10min, slowly add 40mL of concentrated sulfuric acid dropwise under stirring, after the addition is complete, stir and reflux for 12h. After the reaction was completed, it was cooled at -20°C for 30 min, suction filtered while cold, and dried to obtain a white solid. Yield: 62.44%, LC-MS: 485.2[M+H]+ .

[0170] Step B: Preparation of methyl 3,11-dioxo-18β-oleanane-12-ene-30-carboxylate

[0171] The title compound was prepared by using the preparation method in Step A of Example 1, substituting 3β-hydroxy-11-oxo-18β-oleanane-12-ene-30-carboxylic acid methyl ester for 18β-glycyrrhetinic acid. L...

Embodiment 3

[0174] Example 3: (E)-2-((3,11-dioxo-18β-oleanane-12-ene-30-carboxylate benzyl ester)-2(1H)-ethylene)-carboxy Preparation of methyl ester

[0175]

[0176] Take 0.3g (0.49mmol) (E)-2-((3,11-dioxo-18β-oleanane-12-ene-30-carboxylate benzyl ester)-2(1H)-ethylene )-Carboxylic acid was placed in a 50mL eggplant-shaped bottle, and then 15mL of thionyl chloride was added to dissolve, and the reaction was stirred at 80°C for 30min. After cooling, the remaining thionyl chloride was evaporated to dryness under reduced pressure, and a small amount of anhydrous dichloromethane was added and evaporated to dryness again, repeating three times. Add 10 mL of dry dichloromethane to the above-prepared acid chloride to dissolve it, and slowly drop it into anhydrous methanol (2 mL) at -5°C. After the addition was complete, the reaction was stirred at room temperature for 30 minutes. Extract, wash twice with saturated sodium chloride solution, and dry over anhydrous sodium sulfate. The solv...

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Abstract

The invention belongs to the technical field of medicine, and specifically relates to 18β-glycyrrhetinic acid derivatives and their optical isomers and pharmaceutically acceptable salts, a preparation method of the derivatives, and a pharmaceutical composition using the derivatives as active ingredients. Application in the preparation of medicines for treating and / or preventing various cancers. The structures of the derivatives represented by the general formula I, their optical isomers and pharmaceutically acceptable salts are as follows: wherein, each variable is as described in the claims and description.

Description

Technical field: [0001] The invention belongs to the technical field of medicine, and specifically relates to 18β-glycyrrhetinic acid derivatives and their optical isomers and pharmaceutically acceptable salts, a preparation method of the derivatives, a pharmaceutical composition using the derivatives as active ingredients, and Use in the preparation of medicines for treating and / or preventing various cancers. Background technique: [0002] According to the analysis report of the World Health Organization (WHO), cancer is currently the disease with the highest mortality rate, and about 14 million people die of cancer every year. Due to environmental factors, public health and bad living habits, the prevalence of cancer is increasing year by year. The prevention and treatment of cancer has become a research hotspot in the field of medicine and health in the world. Natural products play an important role in the discovery of drugs and the development of medicine, especially i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J63/00A61K31/56A61K31/58A61P35/00A61P35/04
CPCA61P35/00A61P35/04C07J63/008
Inventor 赵临襄刘丹黄敏李爱花魏云飞景永奎
Owner SHENYANG PHARMA UNIVERSITY