Benzo-azepine type derivative and preparation method and purpose thereof

A technology of benzonitrogen and its derivatives, which is applied in the field of medicine and can solve problems such as low cure rate

Inactive Publication Date: 2013-02-06
TIANJIN UNIV OF COMMERCE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the chemotherapy method is relatively fast, the cure rate is very low. At the same time, clinical research has found that there are great deficiencies in the currently used anticancer drugs. Finding new anticancer drugs has become a hot spot in new drug research

Method used

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  • Benzo-azepine type derivative and preparation method and purpose thereof
  • Benzo-azepine type derivative and preparation method and purpose thereof
  • Benzo-azepine type derivative and preparation method and purpose thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Preparation of Intermediate III-1:

[0071]

[0072] Add 3.91g (20mmol) of 7-chloro-3,4-dihydro-1H-benzo[b]azepine-5(2H)-one and 50mL of pyridine into the reaction flask equipped with stirring, thermometer and condenser , stir to dissolve, add 2.91g (24mmol) of 2-chloroethylsulfonyl chloride dropwise at 0°C, keep stirring at -10°C-5°C for 4h, TLC detection shows that the reaction is complete (developing agent: ethyl acetate: petroleum ether = 1: 3).

[0073] The reaction solution was poured into 200ml of 25°C cold water, stirred, and solids were precipitated. After filtering, the filter cake was washed with water and dried to obtain a brownish yellow solid crude product. The crude product was recrystallized with isopropanol to obtain an off-white solid which is intermediate III-1, with a purity of 98.1% (HPLC normalization method), and a yield of 81.0%. ES I-MS: 321.0.

Embodiment 2

[0075] Preparation of Intermediate III-2:

[0076]

[0077] Add 4.58g (20mmol l ), add acetonitrile 50mL, potassium bicarbonate 5.0g (50mmol) and stir, stir at 0°C, add 2.91g (24mmol) of 2-chloroethylsulfonyl chloride dropwise, keep stirring at 5°C-20°C for 3h, TLC detection shows The reaction ends (developing solvent: ethyl acetate: petroleum ether = 1:3).

[0078] The reaction solution was poured into 200 mL of distilled water at 10°C, extracted with ethyl acetate three times, 50 mL each time, dried over anhydrous sodium sulfate, evaporated to dryness, and silica gel column chromatography to obtain a white solid as Intermediate III-2 with a purity of 99.7% (HPLC Normalization method), the yield was 85.8%. ES I-MS: 355.1.

Embodiment 3

[0080] 1-(2-(Dipropylamino)ethylsulfonyl)-7-chloro-3,4-dihydro-1H-benzo[b]azepine-5(2H)-one and compound Ⅰ-1 Preparation of:

[0081]

[0082] Add 3.22g (10mmol) intermediate III-1, 2.0g (20mmol) potassium bicarbonate, 2.02g (20mmol) dipropylamine and 50mL acetonitrile into the reaction flask equipped with stirring, thermometer and condenser, and stir , react at 80°C-90°C for 12 hours, cool to room temperature naturally, filter out insoluble matter, pour the filtrate into 100mL distilled water, extract 3 times with ethyl acetate, 50mL each time, combine the organic phases, and wash the organic phases with saturated brine 3 times , 50 mL each time, dried over anhydrous sodium sulfate, evaporated the solvent under reduced pressure, obtained white solid compound Ⅰ-1 by silica gel column chromatography, purity 99.2% (HPLC normalization method), yield 81.6%, HRMS (m / z)[M+H] + : 387.1504.

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Abstract

The invention discloses a benzo-azepine type derivative and a preparation method and purposes thereof. The benzo-azepine type derivative has the structure of a general formula I, wherein in the formula I, R1 is any one among hydrogen, halogen, or halogen substituted C1-C4 alkyl, R2 is oxygen or hydroxyl, and R3 is any one among hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen or hydroxyl. According to the invention, compounds or pharmaceutically acceptable salts having the structure of the formula I are novel in chemical constitution, and have an obvious restraining effect, the same as fluorouracil generally used in clinical trials, for tumors, in particular to human lung adenocarcinoma cells, human breast cancer cells and human gastric carcinoma cells.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a class of benzazepine derivatives and a preparation method and use thereof. Background technique [0002] Cancer has become a major chronic disease that seriously endangers human health. According to statistics, there are 9 million people who suffer from cancer every year in the world, and 6 million patients die from cancer. Almost one cancer patient dies every second. The annual incidence of cancer in my country is about 1.2 million, the number of cancer deaths is as high as more than 900,000, and the number of patients waiting for treatment exceeds 1.5 million, and there is an increasing trend year by year. Therefore, cancer has become the second largest killer after cardiovascular disease. [0003] Clinically, tumors are treated in three major ways: surgery, radiotherapy, and chemotherapy. Although the chemotherapy method is quicker, the cure rate is very low. At the same...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D223/16A61K31/55A61P35/00
Inventor 梁艳书朱英杰丛萌郭桂梅支爽祁浩飞
Owner TIANJIN UNIV OF COMMERCE
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