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Matrine derivatives and sophoridine derivatives containing aryl amidine or aminoquinoline structure and preparation method thereof

A technology for matrine and sophoridine, which is applied to matrine derivatives and sophoridine derivatives containing aryl amidine or aminoquinoline structures and their preparation fields, can solve the problems of not having too much activity and the like, and achieves the Strong inhibitory effect, high antitumor activity effect

Active Publication Date: 2020-09-08
GUANGXI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the study of important monomers in compound matrine injection, it was found that single compounds such as matrine and sophoridine did not have much activity by themselves, and the combination of multiple compounds may be effective, and it also means a lot. less side effects

Method used

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  • Matrine derivatives and sophoridine derivatives containing aryl amidine or aminoquinoline structure and preparation method thereof
  • Matrine derivatives and sophoridine derivatives containing aryl amidine or aminoquinoline structure and preparation method thereof
  • Matrine derivatives and sophoridine derivatives containing aryl amidine or aminoquinoline structure and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0014] The preparation method of compound JM-01, the steps are as follows:

[0015] (1) Dissolve 5 mmol (1.24 g) of matrine in 30 ml of dichloromethane (DCM), and add 2 eq (10 mmol) of phosphorus oxychloride (POCl) dropwise under stirring at room temperature 3 ), after the solution changed from colorless to light yellow, put it in an oil bath at 60°C and stir and reflux for 1-3 hours until the solution turned brownish red.

[0016] (2) Return the solution to room temperature, and add 1 to 1.5 eq (5 to 7.5 mmol) of aniline in DCM dropwise while stirring, and place the solution in an oil bath at 60° C. to stir and reflux for 12 hours after the dropping.

[0017] (3) After the reaction is completed, return the solution to room temperature, slowly add cold NaOH solution or NaHCO dropwise under stirring 3 Saturated solution, neutralized the pH of the reaction solution to 8-9, stirred for 10 min, extracted three times with water and DCM, and combined the organic phases.

[0018] (...

Embodiment 2

[0149] The preparation method of compound JM-30, the steps are as follows:

[0150] (1) Dissolve 5 mmol (1.24 g) of matrine in 30 ml of dichloromethane (DCM), and add 2 eq (10 mmol) of phosphorus oxychloride (POCl) dropwise under stirring at room temperature 3 ), after the solution changed from colorless to light yellow, put it in an oil bath at 60°C and stir and reflux for 1-3 hours until the solution turned brownish red.

[0151] (2) Return the solution to room temperature, and add 1 to 1.5 eq (5 to 7.5 mmol) of a DCM solution of 2-cyanoaniline dropwise while stirring, and continue to place the solution in a 60°C oil bath for stirring Reflux for 12h.

[0152] (3) After the reaction is completed, return the solution to room temperature, slowly add cold NaOH solution or NaHCO dropwise under stirring 3 Saturated solution, neutralize the pH of the reaction solution to 8-9, stir for 10 min, extract with water and DCM three times, and combine the organic phases.

[0153] (4) Co...

Embodiment 3

[0185] The present invention also includes the application of the imine and aminoquinoline derivatives in the preparation of antitumor drugs. Preferably, the tumors are liver cancer (HepG2) and cervical cancer (HeLa).

[0186] Experimental method: the above-mentioned imine and aminoquinoline derivatives were dissolved and diluted with dimethyl sulfoxide (DMSO) to form a 100um mother solution. During the experiment, the mother solution was diluted with the culture medium to the concentration required for the test. Take a bottle of logarithmic growth cells, digest with trypsin, centrifuge, resuspend, and count under a microscope. According to the counting results, the cells were seeded in a 96-well plate at a density of 5000 cells per well (100 ul medium), and placed in an incubator for 24 hours. After the cells adhered to the wall, the medium was carefully sucked away, and the medium containing different concentrations of the drug to be tested was added to culture for 44 hour...

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Abstract

The invention discloses matrine and sophoridine derivatives containing an arylamidine or aminoquinoline structure and a preparation method thereof. According to the invention, the derivatives are prepared by using matrine or sophoridine as a starting material; the matrine or the sophoridine is subjected to catalytic heating and then undergoes a dehydration reaction with arylamine to form an iminederivative containing an arylamidine structure; and the 2-cyanophenyl-containing imine derivative is cyclized into an aminoquinoline derivative under base catalysis. The prepared derivatives are subjected to activity screening and evaluation through in-vitro pharmacological activity experiments. The preparation method provided by the invention has the advantages of easily-available raw materials,simple operation, mild reaction conditions and high yield; and in-vitro pharmacological experiment results show that the aminoquinoline derivatives have strong inhibitory effect on the proliferation of a variety of cancer cells, and have application potential in clinical tumor research.

Description

technical field [0001] The present invention relates to the synthesis of matrine imine and aminoquinoline derivatives, the synthesis of sophoridine imine and aminoquinoline derivatives, and the application of these compounds in antitumor research. Background technique [0002] Matrine (matrine) and sophoridine (sophoridine) are two important biological total alkaloids extracted from dried roots, plants, and fruits of legumes such as Sophora flavescens, Sophora flavescens, and Sophora japonica through organic solvents such as ethanol. body. In addition to matrine and sophoridine, total alkaloids also contain various alkaloids such as sophocarpine and oxysophocarpine. Matrine and sophoridine are quinolizidine alkaloids with four rings. The structural difference is that the C-5 hydrogen atom of matrine is in S configuration, while the C-5 hydrogen atom of sophoridine is R configuration. The appearance of pure matrine is white powder, and the appearance of pure sophoridine is...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/22A61P35/00
CPCA61P35/00C07D471/22
Inventor 王立升敬德旺王浩东许亦明吴黎川刘旭江俊
Owner GUANGXI UNIV
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