Anti-osteoporosis acacetin derivative and preparation method thereof

An anti-osteoporosis and acacetin technology, which is applied in bone diseases, drug combinations, organic chemistry, etc., can solve the problems of decreased oral bioavailability, poor solubility of acacetin, and inability to fully dissolve, so as to be beneficial to osteoporosis. The deposition, post-processing is simple, the effect of environmental pollution is small

Inactive Publication Date: 2021-06-01
张洪胜
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the solubility of acacetin in water is very poor, so that it cannot be fully dissolved in the aqueous solution of the gastrointestinal tract, and the dissolution rate is reduced, which eventually leads to a decrease in its oral bioavailability. Drugs with poor water solubility usually require high doses to be released after oral administration. Reach therapeutic plasma concentrations, but high doses of drugs may have certain side effects on the human body

Method used

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  • Anti-osteoporosis acacetin derivative and preparation method thereof
  • Anti-osteoporosis acacetin derivative and preparation method thereof
  • Anti-osteoporosis acacetin derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Under nitrogen protection, dissolve 15g acacetin and 14.8g 2,4-dimethoxybenzyl chloride in 78mL of anhydrous dichloromethane, raise the temperature to 110-120°C, and reflux under the action of triethylamine After 8 hours of reaction, cool to room temperature, add 30-40 mL of ethyl acetate to the reaction liquid for extraction and separation, combine the organic phases, dry with anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure to obtain crude products that are separated by silica gel column chromatography , using petroleum ether-ethyl acetate for gradient elution, the volume ratio of petroleum ether to ethyl acetate is 60:1, 40:1, 20:1, 10:1, 5:1, 1:1, TLC detection, The same fractions were combined to obtain a total of 10 fractions, and the fourth fraction was subjected to silica gel column chromatography, using petroleum ether-ethyl acetate 10:1, 5:1 gradient elution, and the collected eluent was recrystallized by ethanol obtain the...

Embodiment 2

[0021] The water solubility test of embodiment 2 compounds of the present invention

[0022] Weigh 0.1 g of the acacetin derivative obtained in Example 1 into a test tube, add 10.0 mL of purified water, shake for 30 seconds every 5 minutes at room temperature, observe the dissolution after 30 minutes, record the amount of solvent, and convert the experimental results into standard solubility (25°C), the test results are shown in Table 1.

[0023] Table 1 Example 1 compound solubility and yield

[0024]

[0025] The results show that, compared with acacetin, the water solubility of the acacetin derivatives is significantly improved, thus indicating that the method of the invention can obtain the acacetin derivatives with better water solubility.

experiment example 3

[0026] Experimental Example 3 Pharmaceutical Research on the Anti-osteoporosis of Compounds of the Present Invention

[0027] Experimental method: select healthy 5-month-old female SD rats, body weight 280 ± 50g, divide the rats into random groups, and divide them into normal control group (control group 1), ovariectomized model group (control group 2), acacetin group ( Control group 3), acacetin derivatives (experimental group), each group of rats was cultivated for 2 weeks in a suitable environment, and each group of female experimental rats was injected with 2% pentobarbital intraperitoneally at a dose of 40 mg / kg body weight After sodium anesthesia, the abdominal cavity of the normal control group was opened and then sutured. The rats in the other groups underwent bilateral ovariectomy. From the third week after the operation, the rats in each group were fed with feed and water every day. Rats in the derivative group were given acacetin and acacetin derivatives at a dose o...

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Abstract

The invention discloses an anti-osteoporosis acacetin derivative and a preparation method thereof, and belongs to the technical field of pharmaceutical chemistry synthesis. The method comprises the following steps: under the protection of nitrogen, adding acacetin and 2,4-dimethoxy benzyl chloride into an organic solvent, reacting for 6-8 hours under the action of alkali, and carrying out silica gel column chromatography separation and recrystallization to finally obtain the acacetin derivative. According to the invention, pathological experiments find that the acacetin derivative can inhibit bone resorption increase and bone tissue destruction caused by lack of female hormone, can also improve the blood calcium concentration and is beneficial to bone deposition, which indicates that the new compound has a certain prevention and treatment effect on osteoporosis caused by lack of female hormone.

Description

technical field [0001] The invention belongs to the technical field of chemical drug synthesis, and relates to an anti-osteoporosis acacetin derivative and a preparation method thereof. Background technique [0002] Acacetin is a natural flavonoid compound widely found in acacia, chrysanthemum, acacia and so on. In addition to the traditional effects of relieving stagnation and calming the nerves, regulating qi and dredging collaterals, acacetin also has the effect of anti-osteoporosis. However, the solubility of acacetin in water is very poor, so that it cannot be fully dissolved in the aqueous solution of the gastrointestinal tract, and the dissolution rate is reduced, which eventually leads to a decrease in its oral bioavailability. Drugs with poor water solubility usually require high doses to be released after oral administration. Reach therapeutic plasma concentrations, but high doses of drugs may have certain side effects on the human body. Therefore, it is necessar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/60A61P19/10
CPCC07D311/60A61P19/10
Inventor 张洪胜
Owner 张洪胜
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