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Hydroxyanthraquinone chlormethine derivative having antitumor activity, and preparation method thereof

A technology for hydroxyanthraquinone nitrogen mustard and antitumor activity, which is applied in the field of hydroxyanthraquinone nitrogen mustard derivatives with antitumor activity and the preparation thereof, can solve problems such as failure to provide nitrogen mustard, and achieves high selectivity and synthetic route. Simple, easy post-processing effects

Inactive Publication Date: 2015-11-11
XUZHOU NORMAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a kind of hydroxyanthraquinone nitrogen mustard derivative with antitumor activity and preparation method thereof, solve the problem that the prior art fails to provide nitrogen mustard through methylene to 1,4-dihydroxyanthraquinone 2 problems of making complexes and carrying out anti-tumor

Method used

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  • Hydroxyanthraquinone chlormethine derivative having antitumor activity, and preparation method thereof
  • Hydroxyanthraquinone chlormethine derivative having antitumor activity, and preparation method thereof
  • Hydroxyanthraquinone chlormethine derivative having antitumor activity, and preparation method thereof

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preparation example Construction

[0022] The preparation method of hydroxyanthraquinone nitrogen mustard derivatives: take 1,4-dihydroxyanthraquinone as raw material, through 2-hydroxyalkylation, then 2-hydroxyalkyl chlorination, and then link with diethanolamine, finally will get The complex is chlorinated with thionyl chloride to obtain the target compound; the specific method is:

[0023] Using 1,4-dihydroxyanthraquinone as a raw material, introduce a hydroxyalkyl group at the 2-position of 1,4-dihydroxyanthraquinone through hydroxyalkylation to obtain 2-(1-substituted-1-hydroxymethyl)-1, 4-dihydroxy-9,10-anthraquinone, and then react with thionyl chloride to chlorinate the hydroxyalkyl to obtain 2-(1-substituted-1-chloromethyl)-1,4-dihydroxy-9,10 -anthraquinone, then react with diethanolamine at room temperature, and finally the resulting 2-(1-substituted-bis(2-hydroxyethylamino)methyl)-1,4-dihydroxy-9,10-anthraquinone React with thionyl chloride to obtain 2-(1-substituted-bis(2-chloroethylamino)methyl)-1...

Embodiment 1

[0033] Example 1: 2-(1-substituted-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinone II1-II18 synthetic general method:

[0034] 1,4-Dihydroxyanthraquinone I (1mmol) was dissolved in methanol (20ml), sodium hydroxide solution (1N, 6ml) was added, and sodium dithionite (2mmol) dissolved in water (2mL) was added under nitrogen. After stirring for 10 minutes, aldehyde (2 mmol) was added and reacted at 0° C. for 3 hours. The reaction solution was poured into 10 mL of ice water added with 30% hydrogen peroxide (2 mL), and stirred for 10 minutes. Add hydrochloric acid solution (3N, 2mL) to acidify, extract with dichloromethane, wash with saturated sodium bicarbonate solution, water, and saturated brine, and dry over anhydrous magnesium sulfate. Separation by column chromatography (dichloromethane) gave orange-red solids II1-II18.

[0035] 2-Hydroxymethyl-1,4-dihydroxy-9,10-anthraquinone II1

[0036] Yield 44%; mp: 208-209°C; 1 HNMR (400MHz, DMSO-d 6)δ13.09(s,1H),12.81(s,1H),8.2...

Embodiment 2

[0071] Example 2: General Synthesis of 2-(1-substituted-1-chloromethyl)-1,4-dihydroxy-9,10-anthraquinone III1-III18:

[0072] Thionyl chloride (1.0 ml) was added to 2-(1-substituted-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinone II (1 mmol). After reacting at 50°C for 2 hours, excess thionyl chloride was distilled off under reduced pressure. The crude product was used directly in the next step without purification.

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Abstract

The invention relates to a hydroxyanthraquinone chlormethine derivative having antitumor activity, and a preparation method thereof, and belongs to an antitumor drug derivative and a preparation method thereof, wherein the hydroxyanthraquinone chlormethine derivative is a 2-(1-substituted-bis(2-chloroethylamino)methyl)-1,4-dihydroxy-9,10-anthraquinone derivative. The preparation method comprises that 1,4-dihydroxyanthraquinone is adopted as a raw material, hydroxyalkyl is introduced into the site 2 of the 1,4-dihydroxyanthraquinone through hydroxyalkylation to obtain 2-(1-substituted-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinone, the 2-(1-substituted-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinone reacts with thionyl chloride to chlorinate the hydroxyalkyl so as to obtain 2-(1-substituted-1-chloromethyl)-1,4-dihydroxy-9,10-anthraquinone, the 2-(1-substituted-1-chloromethyl)-1,4-dihydroxy-9,10-anthraquinone reacts with diethanolamine at a room temperature, and finally the produced 2-(1-substituted-bis(2-hydroxyethylamino)methyl)-1,4-dihydroxy-9,10-anthraquinone reacts with thionyl chloride to obtain the 2-(1-substituted-bis(2-chloroethylamino)methyl)-1,4-dihydroxy-9,10-anthraquinone derivative. The compounds of the present invention have good antitumor activity.

Description

technical field [0001] The invention relates to a derivative used for antitumor drugs and a preparation method thereof, in particular to a hydroxyanthraquinone nitrogen mustard derivative with antitumor activity and a preparation method thereof. Background technique [0002] Nitrogen mustards are a class of antineoplastic drugs widely used clinically, such as cyclophosphamide, chlorambucil, and formyl sarcoid. This type of drug has the advantages of broad anti-tumor spectrum and strong lethality to tumor cells, but it also has disadvantages such as poor selectivity, low treatment efficiency, and large toxic and side effects. The structure of nitrogen mustards generally consists of two parts: an alkylating part and a carrier part. The alkylation part is the functional group of anti-tumor activity, and the carrier part can be used to improve the pharmacokinetic properties such as absorption and distribution of the drug in the body, improve the selectivity and activity of the ...

Claims

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Application Information

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IPC IPC(8): C07C225/36C07C221/00A61P35/00
Inventor 赵立明马凤燕
Owner XUZHOU NORMAL UNIVERSITY
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