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Salicyloyl anilines compound as well as preparation method and application thereof

A technology of salicylanilide and compound, which is applied in the field of pharmaceutical compounds, can solve the problems of being different, cannot increase the curative effect, etc., and achieves the effects of high inhibitory activity and simple preparation

Inactive Publication Date: 2011-11-23
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, several confusions and problems have emerged in research and practice. For example, the monoclonal antibody cetuximab, which is also an EGFR blocking agent, and the small molecule compounds gefitinib and erlotinib, when combined with chemotherapy drugs It shows completely different results when using
The former shows a synergistic effect with chemotherapy drugs in colon cancer and head and neck tumors, and can even reverse chemotherapy resistance; while the latter cannot increase the efficacy of current best chemotherapy drugs at all in the treatment of advanced NSCLC

Method used

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  • Salicyloyl anilines compound as well as preparation method and application thereof
  • Salicyloyl anilines compound as well as preparation method and application thereof
  • Salicyloyl anilines compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1, prepare the salicylanilide compound of the following general formula, wherein R1=R2=methoxyethoxyl group, according to the following preparation method:

[0034]

[0035] Synthesis of Intermediate 2:

[0036] Compound 1 (1.0g, 5.5mmol), methoxybromoethane (1.5mL, 16.5mmol) and K 2 CO 3 (2.3g, 16.5mmol) was dissolved in DMF (30mL), heated to 90-100°C and stirred for 9h. The reaction progress was detected by TLC. After the reaction was completed, the DMF was evaporated to dryness. The residue was extracted with diethyl ether (100 mL), and the combined extracts were washed successively with distilled water (30 mL) and saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness to obtain a yellow liquid, which was poured into petroleum ether (20 mL) , placed in a refrigerator to cool, a white solid was precipitated, suction filtered, and the filter cake was dried to obtain 1.4 g of white solid 56, with a...

Embodiment 2

[0055] Example 2, prepare salicylanilide compounds with the following general formula, wherein when R1 is substituted by 5-methanesulfonylethylaminomethylfuran, R2=hydrogen, R4 is hydrogen, chlorine, methyl, methoxy, R3 Take macromolecule substituents or small molecule substituents as an example:

[0056]

[0057] Synthesis of intermediates 17a-h:

[0058] Dissolve 5-iodosalicylic acid 11 (527.0 mg, 2.0 mmol) in tetrahydrofuran (8 mL), then add 7 [or 2.0 mmol of 8, or 9, or 12, or 13, or 14, or 15, or 16 ], and 5 drops of DMF, EDC·HCl (460.0mg, 2.4mmol) and HOAt (327.0mg, 2.4mmol) were added under ice-bath stirring, and the temperature was stirred for 15min and then returned to room temperature and stirred for 24h. The solvent was evaporated under reduced pressure, diluted with dichloromethane (200mL), washed with distilled water (3×100mL) and saturated brine (3×100mL) successively, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness. ...

Embodiment 3

[0087] Embodiment 3, biological activity assay

[0088] With Lapatinib as the positive control drug, the inhibitory activity of the above-mentioned salicylanilide compounds to EGFR and HER-2 was tested, and its half inhibitory concentration (IC 50 ) as shown in the table below:

[0089]

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Abstract

The invention belongs to the field of medical compounds and relates to a salicyloyl anilines compound as well as a preparation method and application in preparing an anti-cancer medicine. According to the method disclosed by the invention, the salicyloyl aniline is taken as a parent and different side-chain substituent groups are introduced into a benzene ring of the parent to prepare the salicyloyl anilines compound of the following formulas, wherein in the formulas, R1, R2, R3 and R4 are defined as an specification. Compared with the Lapatinib, the prepared salicyloyl anilines compound represents that the IC50 value is obviously reduced or is at least equal to that of the Lapatinib. The experiment shows that the salicyloyl anilines compound provided by the invention has an obvious inhibition effect on tumor cells, especially ovarian cancer cells so that the salicyloyl anilines compound can be further used for preparing antitumor medicines. The chemical formula of the salicyloyl anilines compound is represented by the following formulas.

Description

technical field [0001] The invention belongs to the field of pharmaceutical compounds, and relates to salicylanilide compounds, a preparation method thereof, and an application thereof in the preparation of antitumor drugs. Background technique [0002] The treatment of malignant tumors has been a worldwide problem for a long time. Most of the treatment measures for tumors in the prior art are realized by finding tumors and destroying them. With the continuous deepening of research on cell signal transduction pathways, people have a deeper understanding of the role of oncogenes and anti-cancer genes in tumor cells, making it possible to design new anti-tumor drugs for specific molecular targets of tumors . [0003] Studies have shown that the protein tyrosine kinase (PTK) signaling pathway is related to the proliferation, differentiation, migration and apoptosis of tumor cells. Interfering or blocking the tyrosine kinase pathway can be used to treat tumors, so screening fo...

Claims

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Application Information

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IPC IPC(8): C07C235/64C07D213/30C07D231/12C07D307/54C07D405/12C07C231/02A61K31/609A61K31/625A61P35/00
Inventor 李英霞张伟丁宁肖华玲
Owner FUDAN UNIV
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