Salicylamide antitumor compound and its synthesis method and application

A technology of salicylamide and a synthesis method, which is applied in the field of antitumor drugs, can solve the problems of easy drug resistance and low efficacy of drugs, and achieve the effects of inhibiting tumor cell proliferation activity, simple structure and easy synthesis method.

Inactive Publication Date: 2011-12-14
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some drugs are found to be ineffective after clinical application, and some drugs that act on a single target are prone to drug resistance

Method used

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  • Salicylamide antitumor compound and its synthesis method and application
  • Salicylamide antitumor compound and its synthesis method and application
  • Salicylamide antitumor compound and its synthesis method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Preparation of 2-hydroxy-5-(7-hydroxyamino-7-oxoheptanyl)-N-phenylbenzamide (1)

[0047] 1A. 5-Nitro-2-hydroxy-N-phenylbenzamide

[0048]Add 2.75g (15mmol) of 5-nitrosalicylic acid, 2.1g (22.5mmol) of aniline, 5.8ml (22.5mmol) of triphenyl phosphite, and 30ml of toluene into a 100ml round bottom flask. Nitrogen protection was used to reflux for 8 hours, the reaction system was cooled to room temperature, and a pale yellow solid was precipitated. Add 20ml of dichloromethane to the system, filter with suction, wash the filter cake with cold dichloromethane (5ml×2), recrystallize from absolute ethanol (20ml) to obtain 3.2g of yellow powder, yield 84%, mp: 219- 221°C. MS: 258.93

[0049] 1B. 5-Amino-2-hydroxy-N-phenylbenzamide

[0050] In a 250ml round bottom flask, add 3.1g (12mmol) of 5-nitro-2hydroxy-N-phenylbenzamide, ethanol (40ml), tetrahydrofuran (40ml), iron powder 6.7g (120mmol), glacial acetic acid (10ml ), the system was refluxed for 7h and cooled ...

Embodiment 2

[0056] Example 2 Preparation of 2-hydroxy-5-(7-hydroxyamino-7-oxoheptanyl)-N-(3-fluorophenyl)benzamide (2)

[0057] 2A.5-Nitro-2-hydroxy-N-(3-fluorophenyl)benzamide

[0058] Same as the synthesis of compound 1A in Example 1, reflux in toluene with 2.38g (13mmol) of 5-nitrosalicylic acid, 1.11g (10mmol) of 3-fluoroaniline, and 3.4ml of triphenyl phosphite to obtain compound 2A, light yellow 2.6 g of white needle crystals, 94% yield, mp: 208-210°C. MS: 276.

[0059] 2B. 5-Amino-2-hydroxy-N-(3-fluorophenyl)benzamide

[0060] Similar to the synthesis of compound 1B in Example 1, using 1.95 g (7 mmol) of compound 2A as a raw material, ethanol, tetrahydrofuran, glacial acetic acid and iron powder were refluxed to obtain the target compound 2B, a gray solid, and the reaction was quantitatively completed. used directly in the next reaction.

[0061] 2C.2-Hydroxy-5-(7-ethoxy-7-oxoheptanyl)-N-(3-fluorophenyl)benzamide

[0062] Same as the synthesis of compound 1C in Example 1, the ...

Embodiment 3

[0065] Example 3 Preparation of 2-hydroxy-5-(7-hydroxyamino-7-oxoheptanyl)-N-(3,4-difluorophenyl)benzamide (3)

[0066] 3A. 5-Nitro-2-hydroxy-N-(3,4-difluorophenyl)benzamide

[0067] With the synthesis of Compound 1A in Example 1, 2.38g (13mmol) of 5-nitrosalicylic acid, 1.29g (10mmol) of 3,4-difluoroaniline, and 3.4ml of triphenyl phosphite were refluxed in toluene to obtain the target Compound 3A, 2.7 g of yellow-green needle crystals, yield 93%, mp: 257-258°C. MS: 294.

[0068] 3B. 5-Amino-2-hydroxy-N-(3,4-difluorophenyl)benzamide

[0069] Same as the synthesis of compound 1B in Example 1, using compound 3A 2.0g (6.8mmol) as raw material, ethanol, tetrahydrofuran, glacial acetic acid and iron powder were refluxed to obtain target compound 3B, off-white solid 1.62g, yield 90%, directly used in Next reaction.

[0070] 3C.2-Hydroxy-5-(7-ethoxy-7-oxoheptanoyl)-N-(3,4-difluorophenyl)benzamide

[0071] Same as the synthesis of compound 1C in Example 1, the compound 3B obtain...

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Abstract

The invention discloses a class of compounds with antitumor activity. The structural formula is as follows: In the formula, R is one or two substituents of ethynyl, chlorine, fluorine, trifluoromethyl and 3-fluorobenzyloxy; X is O or NH; Y is CH2 or CO (carbonyl); Z is H or methoxy; n=5 or 6. The salicylic amide compounds in the structural formula are synthesized from 5-nitrosalicylic acid or 4-methoxysalicylic acid and aniline derivatives through amidation, reduction, and reaction with monoethyl pimelic acid chloride. . The compound has a novel structure and the synthesis method is easy to realize. The anti-tumor activity test showed that it has inhibitory effect on the growth of human liver cancer cells (HepG-2), human colon cancer (SW 480) and human prostate cancer cells (PC3), and the activity of most compounds is stronger than that of gefitinib. The use of preparing anti-tumor drug preparations.

Description

technical field [0001] The invention belongs to the field of antineoplastic drugs, and relates to an antineoplastic compound, in particular to a class of salicylamide antineoplastic compounds containing a hydroxamic acid structure at the 5-position, a synthesis method and an application for preparing antineoplastic drugs. Background technique [0002] Tumors are a serious threat to human health. In the past 20 years, the mortality rate of cancer in my country has increased by 29.42%. [0003] At present, the treatment methods for tumors are still traditional surgery, radiation therapy and drug therapy, but to a large extent, drug therapy is still the main method. Therefore, it is of great significance to research and develop new antitumor drugs. [0004] In recent years, with the progress of tumor molecular biology research, more understanding of tumor pathogenesis has been obtained, and many new targets of anti-tumor drugs have been found, which has made many new achieveme...

Claims

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Application Information

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IPC IPC(8): C07C259/06A61K31/609A61P35/00
Inventor 张三奇左淼吕社民郑悦雯宣伟
Owner XI AN JIAOTONG UNIV
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