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Norabieta cantharidin derivant and synthesis thereof

A technology of demethylcantharidin and a synthesis method, which is applied in the directions of sugar derivatives, drug combinations, pharmaceutical formulations, etc., can solve the problems of low encapsulation rate, difficult liver targeting, etc., and achieves reduction of dosage and improvement of therapeutic effect. , the effect of high yield

Inactive Publication Date: 2011-08-10
SUZHOU UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Before the present invention was made, the publication number was CN1927169 Chinese invention patent "norcantharidin magnetic nano-microspheres and preparation method thereof", a method for preparing norcantharidin magnetic nano-microspheres was provided, which used biological Degradable polymer as carrier, nano-Fe 3 o 4 As magnetic seeds, magnetic nanospheres wrapped with norcantharidin were prepared by using the composite emulsion-solvent evaporation method, but the encapsulation efficiency of the drug was only 8-15%; due to the strong water solubility of norcantharidin, its Encapsulated in passive targeting drug carrier systems such as nanoparticles, liposomes and other carriers, the encapsulation efficiency is low, and it is difficult to form effective therapeutic liver targeting
At present, there is no report of connecting norcantharidin with lactobionic acid to obtain new derivatives with liver targeting at home and abroad.

Method used

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  • Norabieta cantharidin derivant and synthesis thereof
  • Norabieta cantharidin derivant and synthesis thereof
  • Norabieta cantharidin derivant and synthesis thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] step 1:

[0025] Anhydrous ethylenediamine (0.8ml, 12mmol) was added dropwise to a methanol solution of norcantharidin (2g, 12mmol), dissolved in an ice bath for 5 minutes, stirred at room temperature for 6 hours, left to stand, filtered, and the filtrate was separated through a column to obtain 1.86 g (8.9 mmol; yield: 73.89%) of white powder, which is norcantharidin monoamide. Melting point: 154-155°C TLC: Rf≈0.5 (ethyl acetate:methanol=4:1); infrared (v / cm -1 ): 3404 (doublet, -NH 2 ), 1689 (singlet-C=O).

[0026] The reaction formula of this step is as follows:

[0027]

[0028] Step 2:

[0029] The sodium lactobionate aqueous solution was passed through a cation exchange column to obtain an aqueous lactobionic acid solution, which was then vacuum-dried at 80°C to obtain white lactobionic acid powder. Its reaction formula is as follows:

[0030]

[0031] Step 3:

[0032] The lactobionic acid (5g, 13.95mmol) that above-mentioned steps obtains is dissolve...

Embodiment 2

[0046] step 1:

[0047] Anhydrous ethylenediamine (8ml, 120mmol) was added dropwise into methanol of norcantharidin (20g, 120mmol), dissolved in an ice bath for 10 minutes, stirred at room temperature for 8 hours, allowed to stand, filtered, and the filtrate was separated by column to obtain a white powder 18.9g (90mmol; yield: 74.68%), namely norcantharidin monoamide. Melting point: 154-155°C; TLC: Rf≈0.5 (ethyl acetate:methanol=4:1); infrared (v / cm -1 ): 3403 (doublet, -NH 2 ), 1688 (singlet-C=O).

[0048] Step 2:

[0049] The sodium lactobionate aqueous solution was passed through a cation exchange column to obtain an aqueous lactobionic acid solution, which was then vacuum-dried at 80°C to obtain white lactobionic acid powder.

[0050] Step 3:

[0051] Lactobionic acid (50g, 139.5mmol) was dissolved in 260ml of ethylene glycol methyl ether at a temperature of 110°C, heated and stirred in an oil bath to dissolve, diluted with 130ml of toluene, concentrated by distillat...

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Abstract

The present invention discloses a norcantharidin derivative and a synthesis method thereof, which belongs to the field of medicine preparation technology. The method utilizes ethylene diamine as a connecting arm to connect norcantharidin with lactobionic acid in order to produce a new compound, and besides anticancer activity, the compound also has good liver-targeting character. The synthesis method is simple, the yield is high, the cost is low, the toxic side effect of the norcantharidin in the treatment of liver cancer can be effectively reduced, the liver is targeted, and the curative effect is improved.

Description

technical field [0001] The invention relates to a heterocyclic compound and its synthesis method, in particular to a demethylcantharidin derivative and its synthesis, and belongs to the technical field of medicine preparation. Background technique [0002] Norcantharidin is artificially synthesized by removing the 1 and 2 methyl groups according to the chemical structure of cantharidin, the anti-tumor active ingredient of cantharidin, an insect of the family Coleoptera. , while maintaining the strong anti-tumor activity of cantharidin and the unique effect of increasing white blood cells. At present, it is mainly used in the treatment of primary liver cancer. The advantages make it widely used. However, adverse reactions such as irritation of the urinary system and gastrointestinal tract reactions may occur when the clinical application dose of the drug is slightly larger. Animal experiments have shown that pathological changes occur in kidney and liver tissues when the do...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H15/04A61K31/7056A61P35/00C07H15/26
Inventor 张学农胡展红周奕章良王钦
Owner SUZHOU UNIV