Chlorin derivative, corresponding preparation method and application thereof

A technology for chlorin and derivatives, applied in the field of chlorin derivatives and their preparation, can solve the problems of difficulty in reflecting clinical value, slow clearance rate, narrow therapeutic window and the like

Active Publication Date: 2020-11-17
GUANGZHOU EEC BIOTECH DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The light and sound sensitizers reported so far show a large difference in selectivity to tumor cells, a short irradiation wavelength, a narrow therapeutic window, poor solubility under physiological conditions, and a slow clearance rate in the body, making it difficult to reflect clinical value.

Method used

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  • Chlorin derivative, corresponding preparation method and application thereof
  • Chlorin derivative, corresponding preparation method and application thereof
  • Chlorin derivative, corresponding preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0236] The preparation of embodiment 1. compound 8-BA and 9-BA (Pd)

[0237] The synthetic route of compound 8-BA and 9-BA (Pd) is as follows:

[0238]

[0239] Each step in the above-mentioned synthetic route is specifically as follows:

[0240] Dissolve 541 mg of compound 1 in 5% sulfuric acid methanol solution, concentration 0.1 M, react for 10 hours and then concentrate under reduced pressure, dilute the obtained acid with an equal volume of dichloromethane (DCM), wash with water, collect the organic phase, and concentrate to obtain compound 2 , directly used in the next reaction without separation.

[0241] Dissolve compound 2, the product of the previous step, in dimethylformamide (DMF) at a concentration of 0.1M, add 435 mg of benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU ) and 189 μL N,N-diisopropylethylamine (DIEA), after stirring for 0.5-1 hour, add 417 mg β-alanine tert-butyl ester hydrochloride and 379 μL DIEA successively, and continue ...

Embodiment 2

[0248] Embodiment 2. The impact of compound 9-BA (Pd) on breast cancer and breast cancer metastasis

[0249] Using the water-soluble chlorin derivative 9-BA(Pd) synthesized in Example 1 as the sonosensitizer (abbreviated as the sonosensitizer), the sonodynamic therapy of breast cancer lung metastasis tumor-bearing mice was evaluated in the sound field .

[0250] The water-soluble chlorin derivative 9-BA(Pd) is dissolved in physiological saline to prepare a drug solution for administration. 4T1 mouse breast cancer cells were inoculated directly under the second pair of nipples on the left side of Balb / c (female, 18-22 g) mice to construct a mouse breast cancer lung metastasis model, and the tumor volume and mouse tumor volume were recorded on the 7th day after inoculation. Body weight was measured every other day. The tumor-bearing mice were randomly divided into 4 groups: (1) a control group (normal saline alone), (2) b ultrasound group, (3) c administration (9-BA(Pd)) group...

Embodiment 3

[0255] Embodiment 3. The preparation of compound 17-MPA and 18-MPA (Pd)

[0256] The synthetic route of compound 17-MPA and 18-MPA (Pd) is as follows:

[0257]

[0258] Each step in the above-mentioned synthetic route is specifically as follows:

[0259] 1000mg of compound 1-chlorin e6 was dissolved in dimethylformamide (DMF) at a concentration of 0.1M, added 1043μL of iodomethane and 4633mg of anhydrous potassium carbonate, stirred for 2 hours, and diluted with dichloromethane (DCM) The reaction solution was washed with water, the collected organic phase was concentrated, and 200-300 mesh silica gel column chromatography was eluted with ethyl acetate / dichloromethane=1:100 to obtain 962 mg of compound 10 with a yield of 90%.

[0260] Dissolve 800 mg of compound 10 and 675 μL of p-methoxystyrene in dichloromethane (DCM) at a concentration of 0.03 M, add 319 mg of Grubbs catalyst, and then reflux for 20 hours. After the reaction solution is filtered, the filtrate is transfer...

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Abstract

The invention relates to a chlorin derivative, a preparation method of the chlorin derivative, a photoacoustic sensitive agent containing the chlorin derivative, an antitumor drug containing the chlorin derivative, and application of the chlorin derivative in preparation of the antitumor drug. The chlorin derivative of the present invention can be used for photodynamic therapy and sonodynamic therapy so as to effectively suppress and treat cancer.

Description

technical field [0001] The present invention relates to a chlorin derivative and a preparation method thereof, a photoacoustic sensitizer comprising the chlorin derivative, an antitumor drug comprising the chlorin derivative, and the chlorin derivative Use of hydroporphine derivatives in the preparation of antitumor drugs. Background technique [0002] Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are to trigger a chemical reaction to kill the Modern medical technology of tumor cells. [0003] Photodynamic therapy (PDT) is a new method of treating tumors or diseases with photosensitizers and laser activation. It uses photosensitizers to generate singlet oxygen ( 1 o 2 ) react with free radicals to kill tumor cells. Compared with traditional treatment methods such as surgery, chemotherapy, and radiotherapy, PDT has the advantages of less side effects on the body and no damage to internal organs, etc., but it is ineffective in the treatment of deep tumors in the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/22A61K41/00A61P35/00A61P35/04
CPCA61K41/0033A61K41/0071A61P35/00A61P35/04C07D487/22
Inventor 赵伟杰Q·李曹雷苏江安王柳王晓怀邵堃于波
Owner GUANGZHOU EEC BIOTECH DEV CO LTD
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