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Di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivative as well as preparation method and application thereof

A double substitution, derivative technology, applied in the field of compounds and their preparation, can solve problems such as toxic and side effects

Active Publication Date: 2013-11-20
HARBIN MEDICAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

At present, most of the chemotherapeutic drugs in clinical use have toxic side effects, inhibit tumor cells and also inhibit normal cells, which brings great pain to cancer patients

Method used

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  • Di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivative as well as preparation method and application thereof
  • Di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivative as well as preparation method and application thereof
  • Di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivative as well as preparation method and application thereof

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preparation example Construction

[0032] The preparation method of the double-substituted dinaphtho[2,1-b:1',2'-d]furan derivatives of the present invention, the steps are as follows:

[0033] (1) Preparation of dinaphtho[2,1-b:1′,2′-d]furan-3,11-dinitrile (compound 2):

[0034] Add 8.5g (20mmol) of 3,11-dibromodinaphthofuran (compound 1), 4.1g (45mmol) of CuCN, and 125mL of DMSO into a 250mL three-neck flask, heat to reflux for 5h, and monitor the reaction by TLC. After the reaction is complete, the reaction system Under stirring, add concentrated ammonia water slowly, filter with suction, wash the filter cake with concentrated ammonia water until the filtrate is colorless, then wash with water and chloroform respectively, and obtain a light yellow solid (compound 2) after drying;

[0035] (2) Preparation of dinaphtho[2,1-b:1′,2′-d]furan-3,11-dicarboxylic acid (compound 3):

[0036] Add 9.5g (30mmol) of compound 2, 4.8g (120mmol) of NaOH, and 80mL of ethylene glycol into a 150mL three-necked flask, and heat to...

Embodiment 1

[0051] Embodiment 1: Preparation of dinaphtho[2,1-b:1′,2′-d]furan-3,11-dicarboxamide (5):

[0052] Add compound 3 (2mmol), chloroform (20mL) and 1 drop of DMF into a 100mL three-necked flask, then add a solution of thionyl chloride in chloroform (4.4mL of thionyl chloride dissolved in 10mL of chloroform), and then heat to reflux for 4h , the system changed from a suspension to a yellow solution, and the solvent was distilled off under reduced pressure to obtain acid chloride 4.

[0053] Add compound 4 and 30mL chloroform into a 100mL three-necked flask, slowly inject excess ammonia into it, react at room temperature for 2 to 3 hours, filter the white precipitate formed by the reaction, wash the precipitate with chloroform and distilled water in turn, and dry in vacuum to obtain compound 5.

[0054] Yield 84.1%.mp 270-272℃. 1 H NMR (400 MHz, DMSO-d 6 )δ:9.11(d,J=8.8Hz,2H,1,13-H),8.80(d,J=1.5Hz,2H,4,10-H),8.30(dd,J=8.9,1.6Hz, 2H,2,12-H),8.27(d,J=9.0Hz,2H,5,9-H),8.24(s,2H,CON...

Embodiment 2

[0055] Example 2: N 3 ,N 11 -Preparation of dimethyl dinaphtho[2,1-b:1′,2′-d]furan-3,11-dicarboxamide (6):

[0056] Add compound 3 (2mmol), chloroform (20mL) and 1 drop of DMF into a 100mL three-necked flask, then add a solution of thionyl chloride in chloroform (4.4mL of thionyl chloride dissolved in 10mL of chloroform), and then heat to reflux for 4h , the system changed from a suspension to a yellow solution, and the solvent was distilled off under reduced pressure to obtain acid chloride 4.

[0057] Methylamine hydrochloride (270mg, 4mmol) and chloroform (25mL) were added to a 100mL three-necked bottle, and a chloroform solution of compound 4 and triethylamine was added dropwise thereto (dissolve the 4 prepared above in 20mL of chloroform, and then Add triethylamine (2 mL), react at room temperature for 2-3 hours after the dropwise addition, filter the white precipitate formed by the reaction, wash the precipitate with chloroform and distilled water in turn, and dry in v...

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Abstract

The invention relates to a di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivative as well as a preparation method and an application thereof. The preparation method comprises the following steps of: synthesizing a series of di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivatives through a series of reactions by using dibromo-dinaphtho-[2,1-b:1',2'-d] furan as the material. The invention further provides an application of the di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivative in preparing an anti-tumor drug. By virtue of in-vitro pharmacological activity screening, the compound which is synthesized by the preparation method disclosed by the invention is shown to have an effect for inhibiting proliferation of tumor cells, wherein the compound 16 has an obvious inhibiting effect for the liver cancer cells SMMC-7721; and the IC50 value reaches 0.57mu M. Besides, the di-substituted dinaphtho-[2,1-b:1',2'-d] furan derivative is reasonable in design, simple and convenient in preparation method and strong in practicability.

Description

technical field [0001] The present invention relates to a class of compounds and their preparation methods and applications, in particular to bis-substituted dinaphtho[2,1-b:1′,2′-d]furan derivatives and their preparation methods and preparation of antitumor drugs The invention belongs to the field of chemical synthesis. Background technique [0002] Malignant tumors are one of the major diseases that endanger human life. According to WHO statistics, about 8 million people die of cancer every year, and more than 20,000 people die of cancer every day. Tumor treatment methods include surgery, radiotherapy, and chemotherapy, but to a large extent, chemotherapy is the main method. Chemotherapy for tumors has made great progress. From single chemotherapy, it has entered the era of combination chemotherapy and comprehensive chemotherapy. For some patients, even curative effects have been achieved. Therefore, chemotherapy plays an increasingly important role in tumor treatment. A...

Claims

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Application Information

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IPC IPC(8): C07D307/77A61K31/343A61P35/00
Inventor 杨宝峰杨异卉吴立军王立波侯云龙宋永彬刘波
Owner HARBIN MEDICAL UNIVERSITY
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