Osthole derivative, its preparation method and its application in preparing medicine for treating breast cancer

A technology of osthole and derivatives, which is applied in the direction of drug combination, antineoplastic drugs, and active ingredients of heterocyclic compounds, etc., which can solve the problems of human body damage, damage to hematopoietic and immune functions, and high price, and achieve fewer synthesis steps and simple reactions , the effect of high yield

Inactive Publication Date: 2011-09-21
SHANGHAI UNIV OF T C M
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As we all know, most of the drugs commonly used in clinical treatment of tumors are highly toxic and have serious damage to the human body, such as cyclophosphamide, cisplatin, etc., which mainly damage hematopoietic and immune functions, and anti-tumor drugs with slightly less toxic side effects are expensive. Higher, such as paclitaxel, etc.

Method used

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  • Osthole derivative, its preparation method and its application in preparing medicine for treating breast cancer
  • Osthole derivative, its preparation method and its application in preparing medicine for treating breast cancer
  • Osthole derivative, its preparation method and its application in preparing medicine for treating breast cancer

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1: the preparation of compound 1

[0033] Add 3.0 g (12.3 mmol) of osthole into a round-bottomed flask with an appropriate volume, dissolve it in 20 mL of ethanol solvent, and then add 85 mg (0.35 mmol) of platinum dioxide. The reaction mixture system is degassed under reduced pressure and then filled with hydrogen. (This process was repeated three times), the reaction mixture was stirred and reacted overnight at room temperature in a hydrogen atmosphere, and after the complete disappearance of the reactant was monitored by thin-plate chromatography, about 30 mL of methanol was added to dilute the reaction solution, filtered, the filtrate was concentrated, and the residue was recrystallized to obtain a white solid (hydrogenated snake Bedsin) about 2.8g, yield 91%.

[0034] UPLC-MS (m / z): 1.81min (247.1, M+1)

[0035] 1 H NMR (400MHz, CDCl 3 ): δ7.82 (1H, d, J = 9.0Hz), 7.18 (1H, d, J = 8.4Hz), 6.53 (1H, d, J = 8.4Hz), 6.34 (1H, d, J = 9.4Hz) , 2.81 (2H, t...

Embodiment 2

[0039] Embodiment 2: the preparation of compound 2

[0040] In the flask, add 100 mg (0.31 mmol) of 3-bromohydroosthole and dissolve in 5 mL of dioxane, then add tetrakis (triphenylphosphine) palladium 36 mg (0.031 mmol), cesium carbonate 202 mg (0.62 mmol), Finally, 100 mg (0.31 mmol) of 3,4-dimethoxyphenylboronic acid was added, the reaction system was filled with nitrogen protection, and the reaction was refluxed at 120 ° C for 12 hours. After thin plate chromatography until the reactant completely disappeared, the reaction solution was cooled to room temperature. The organic phase was diluted with ethyl acetate, washed with water and saturated brine successively, dried over anhydrous sodium sulfate and filtered. The organic phase was concentrated under reduced pressure to remove the solvent, and the residue was subjected to silica gel column chromatography (eluent: acetone / petroleum ether=1 / 5) to obtain 50 mg of a white solid (compound 2), with a yield of 42%.

[0041] UP...

Embodiment 3

[0043] Embodiment 3: the preparation of compound 3

[0044] In the flask, add 80 mg (0.25 mmol) of 3-bromohydroosthole and dissolve in 5 mL of dioxane, then add 30 mg (0.025 mmol) of tetrakis(triphenylphosphine) palladium, and 163 mg (0.50 mmol) of cesium carbonate, Finally, 71mg (0.37mmol) of 4-trifluoromethylphenylboronic acid was added, the reaction system was filled with nitrogen protection, and the reaction was refluxed at 120°C for 15 hours. The reaction was monitored by thin-plate chromatography until the reaction was complete. The reaction solution was cooled to room temperature and diluted with ethyl acetate. The organic phase was successively washed with water and saturated brine, dried over anhydrous sodium sulfate and filtered. The organic phase was concentrated under reduced pressure to remove the solvent, and the residue was subjected to silica gel column chromatography (eluent: acetone / petroleum ether=1 / 5) to obtain 40 mg of a white solid (compound 3), with a yi...

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PUM

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Abstract

The invention discloses a novel osthole derivative which is a compound having a structure of formula I or formula II. The invention further discloses a preparation method of the osthole derivative comprising that the osthole derivative as an initial raw material undergoes a hydrogenation reduction reaction; a product of the hydrogenation reduction reaction is reacted with N-bromo succinimide (NBS) and then bromine is introduced into the product; and the bromination product undergoes a coupling reaction with multiple boracic acids in the presence of palladium catalysts and thus a series of osthole derivatives are obtained. The invention further discloses an application of the osthole derivative in preparing medicine for treating breast cancer, wherein the osthole derivative exhibits IC50 values of 0.2 to 50 micrometers for inhibitions of breast cancer cells MCF-7 and thus has strong inhibition effects for breast cancer cells MCF-7.

Description

technical field [0001] The invention relates to osthole derivatives, which have inhibitory effect on MCF-7 cells, some of which have obvious inhibitory effect, and can be used to prepare lead compounds of drugs for treating breast cancer. The invention also relates to the preparation method of the osthole derivative and its application in the preparation of anti-breast cancer drugs. Background technique [0002] Cnidium monnieri (Cnidium monnieri (L.) Cusson) is the dry and mature fruit of Cnidium monnieri (L.) Cusson in the Umbelliferae family (Umbelliferae). It grows and distributes in various regions of my country, and its natural resources are very rich. Fructus Cnidii is warm in nature, bitter in taste, returns to the kidney meridian, and has a small poison. It is used externally to remove dampness, kill parasites and relieve itching, orally, to warm the kidney and strengthen yang, to dispel wind and dry dampness. For the treatment of impotence, cold uterus, lumbago d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/16A61K31/37A61P35/00
Inventor 尤丽莎王新宏安睿
Owner SHANGHAI UNIV OF T C M
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