Desloratadine-containing amino acid derivative as well as preparation method and application thereof

A technology of chloromethyl and phenyl, which is applied in the field of anti-tumor compounds and their preparation, and can solve problems such as damage, mutagenesis, and side effects

Active Publication Date: 2013-04-17
TIANJIN INSTITUTE OF PHARMA RESEARCH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chemotherapy is faster, but the cure rate is very low
At the same time, it is clinically found that many anticancer drugs have obvious damage and side effects on the normal body, such as mutagenesis and genotoxicity

Method used

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  • Desloratadine-containing amino acid derivative as well as preparation method and application thereof
  • Desloratadine-containing amino acid derivative as well as preparation method and application thereof
  • Desloratadine-containing amino acid derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0051] Preparation of intermediate Ⅲ-1

[0052]

[0053] In the reaction flask equipped with stirring, condenser and thermometer, add 3.10g (10mmol) desloratadine (II) and 30ml of dichloromethane, stir, control the temperature at 0°C, add 2.5g (12mmol) of DCC in batches ) and a catalyst amount of DMAP, after stirring for 1 hour, slowly add 0.76 g (10 mmol) of glycolic acid dropwise, react at 0°C for 3 hours, filter the insoluble matter, and the filtrate is sequentially washed with 10% dilute hydrochloric acid (15ml×3), 10% sodium bicarbonate aqueous solution (15ml×3), washed with saturated brine (15ml×3), filtered off the insoluble matter, dried the filtrate with anhydrous sodium sulfate, evaporated the solvent under reduced pressure, and separated the residue by silica gel column chromatography to obtain a white solid, which was collected Yield 77.5%, purity 95.5% (HPLC normalization method), ESI-MS (m / z): 368.1.

Embodiment 2

[0055] Preparation of Intermediate III-2

[0056]

[0057] In the reaction flask equipped with stirring, condenser and thermometer, add 3.10g (10mmol) desloratadine (II) and 30ml of dichloromethane, stir, control the temperature at 0°C, add 2.5g (12mmol) of DCC in batches ) and a catalytic amount of DMAP, after stirring for 1 hour, slowly add 1.04 g (10 mmol) of 4-hydroxybutyric acid dropwise, react at 0°C for 3 hours, filter the insoluble matter, and wash the filtrate with 10% dilute hydrochloric acid (15ml×3), 10% carbonic acid Wash with sodium hydrogen aqueous solution (15ml×3) and saturated brine (15ml×3), filter off the insoluble matter, dry the filtrate with anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and separate the residue by silica gel column chromatography to obtain white Solid, yield 75.8%, purity 97.5% (HPLC normalization method), ESI-MS (m / z): 396.2.

Embodiment 3

[0059] Preparation of intermediate Ⅳ-1

[0060]

[0061] In a reaction flask equipped with stirring, condenser, and thermometer, add 3.68g (10mmol) of intermediate III-1, 50ml of pyridine and stir to dissolve it. The solution is controlled below -5°C, and 2.28g (12mmol) of Toluenesulfonyl chloride was reacted at 0°C for 10 hours. TLC showed that the reaction was complete. Pour the reaction solution into cold water, and a solid precipitated out. After filtration, the filter cake was washed with saturated brine (50ml×3), and dried in vacuo to obtain a white solid. Yield 92.2%, purity 98.0% (HPLC normalization method), ESI-MS (m / z): 522.1.

[0062] Reference Example 4:

[0063] Preparation of intermediate IV-2

[0064]

[0065] Add 3.96g (10mmol) of intermediate III-2, 50ml of N,N-dimethylformamide and 2.52g (25mmol) of triethylamine into a reaction flask equipped with stirring, condenser, and thermometer, stir to dissolve , the solution is kept below -5°C, add 2.28g (...

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PUM

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Abstract

The invention discloses a desloratadine-containing amino acid compound with a structure of formula I and a pharmaceutically acceptable salt thereof. In the formula, n is 1, 2 or 3, m is 0, 1, 2, 3, 4, 5 or 6, and R is hydrogen, methyl, ethyl, isopropyl, fluorine-substituted C1-C4 alkyl or chloromethyl. The invention further discloses a preparation method for the compound and a pharmaceutical composition taking the compound or the pharmaceutically acceptable salt of the compound as an active ingredient at the same time, as well as the application of the compound, the pharmaceutically acceptable salt of the compound and the pharmaceutical composition serving as anti-tumor drugs, especially the application in preparation of drugs for treating breast cancer, lung cancer and gastric cancer.

Description

technical field [0001] The invention belongs to the technical field of medicine, more specifically, relates to a class of compounds with anti-tumor effect and their preparation method and application. 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. Clinically, tumors are treated in three major ways: surgery, radiotherapy, and chemotherapy. Although the chemotherapy method is quicker, the cure rate is very...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/04A61K31/4545A61P35/00
Inventor 刘登科刘颖支爽祁浩飞田军路亮王景阳
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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