Oleanolic acid derivatives, and preparation method and application thereof

A compound and pharmaceutical technology, applied in the field of medicine, can solve the problems of large gastrointestinal damage, liver toxicity, weight gain, etc., and achieve a significant effect of lowering blood sugar

Active Publication Date: 2012-12-26
TIANJIN INSTITUTE OF PHARMA RESEARCH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These drugs have a good curative effect, but still have the disadvantage of poor tolerance. At the same time, the biggest side effect of many drugs is hypoglycemia. In addition, long-term use can cause great damage to the gastrointestinal tract, which can easily cause indigestion, weight gain, and liver toxicity. Many adverse reactions

Method used

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  • Oleanolic acid derivatives, and preparation method and application thereof
  • Oleanolic acid derivatives, and preparation method and application thereof
  • Oleanolic acid derivatives, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Reference Example 1: Synthesis of Intermediate II

[0044]

[0045] Add 4.57g (0.01mol) of oleanolic acid into a reaction flask equipped with a stirring, condenser, and thermometer, then add 20mL of thionyl chloride to dissolve it, heat up to reflux reaction, and stop the reaction after no acid gas is released. Evaporate thionyl chloride under reduced pressure to obtain intermediate Ⅱ.

[0046] Example 1: Synthesis of Compound Ⅰ-1

[0047]

[0048] Add 4.75g of intermediate II to a reaction flask equipped with a stirring, condenser and thermometer, add 20mL of propionic acid to dissolve it, and add an appropriate amount of concentrated sulfuric acid, reflux reaction, and TLC to control the reaction process. After the reaction, the reaction solution was cooled to -10°C, and triethylamine was added to neutralize the acid in the reaction system until the reaction solution was alkaline. Add 30 mL of dichloromethane, and add 1.44 g (0.01 mol) of 2-amino-4-carboxyt...

Embodiment 2

[0049] Example 2: Synthesis of Intermediate Ⅰ-2

[0050]

[0051] Add 4.75g of Intermediate II into a reaction flask equipped with a stirring, condenser and thermometer, add 20mL of butyric acid to dissolve it, and add an appropriate amount of concentrated sulfuric acid, and reflux the reaction. TLC controls the reaction process. After the reaction, the reaction solution was cooled to -5°C, and pyridine was added to neutralize the acid in the reaction system until the reaction solution was alkaline. Add 30 mL of chloroform, and add 1.90 g (0.01 mol) of 2-amino-4-phenyl-5-methylthiazole in batches under stirring. After the addition, the temperature is raised to reflux and the reaction is continued for 1.5 h (the plate shows that the reaction is complete). Wash the reaction solution with 3×30mL water, separate the chloroform layer, fully dry it with anhydrous sodium sulfate, filter, and evaporate the chloroform under reduced pressure to obtain a light yellow solid product, ...

Embodiment 3

[0052] Example 3: Synthesis of Intermediate Ⅰ-3

[0053]

[0054] Referring to the method of Reference Examples 1 and 2, the esterification reaction occurred with intermediate II and n-valeric acid. After the reaction, the reaction solution was cooled to 0°C, pyridine and dichloromethane were added, and 2-amino-5-trifluoromethylthiazole was added in batches under stirring. After the reaction, the reaction solution was washed with water, and the chloroform layer was separated. Fully dry with anhydrous sodium sulfate, filter, and evaporate chloroform under reduced pressure to obtain a yellow solid product, which is refined with ethyl acetate-petroleum ether to obtain 2.4 g of a white solid product (HPLC: 99.6%), yield 34.7% . Rf=0.44[single point, developer: v(petroleum ether):v(ethyl acetate)=4:1]. MS, m / Z: 691.4 (M+1).

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PUM

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Abstract

The invention belongs to the technical field of medicines capable of lowering blood sugar, and provides oleanolic acid derivatives disclosed as Formula I and salts thereof, wherein n=1, 2, 3 or 4; and R1 and R2 can be hydrogen, C1-C4 straight-chain or branched-chain alkyl group, carboxyl group, phenyl group, halogen or halogenated methyl group, or R3 is straight-chain or branched-chain alkyl group. The invention also relates to a preparation method of the compounds and salts thereof, a medicinal composition which uses the compounds as active effective constituents, and application of the compounds in medicines for lowering blood sugar.

Description

technical field [0001] The invention belongs to the technical field of medicine, more specifically, relates to a preparation method and application of a class of compounds with hypoglycemic effect and salts thereof. Background technique [0002] Oleanic acid (OA) is also known as soil angelica acid and Qingsisu. It exists widely in nature in the free form or combined into glycosides. Especially in plants such as the whole grass of green leaves, privet fruit, hedyotis diffusa, hawthorn, clove, jujube, loquat leaves, and Prunella vulgaris. OA is an oleane-type pentacyclic triterpenoid compound, white needle-like crystal, insoluble in water, soluble in ethanol, chloroform, ether, acetone, due to its wide distribution in nature and its complex structure, it is difficult to synthesize artificially. At present, it is mainly extracted from Chinese medicinal plants. A large number of studies at home and abroad have shown that OA has pharmacological effects such as protecting the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J63/00A61K31/58A61P3/10
Inventor 刘颖刘登科穆帅张大帅牛端吴疆邹美香
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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