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5-substituted dihydrobenzofuran-imidazolium salt compound and preparation method thereof

The technology of a salt compound and benzimidazole is applied in the application field of anti-cancer, which can solve the problems of lack of manufacturing methods, etc.

Inactive Publication Date: 2013-11-27
YUNNAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is still a lack of 5-substituted dihydrobenzofuran-imidazolium salt compounds that use 5-substituted dihydrobenzofuran to produce anti-cancer applications, and there is also a lack of effective manufacturing methods

Method used

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  • 5-substituted dihydrobenzofuran-imidazolium salt compound and preparation method thereof
  • 5-substituted dihydrobenzofuran-imidazolium salt compound and preparation method thereof
  • 5-substituted dihydrobenzofuran-imidazolium salt compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 11-(5-Methyl-substituted dihydrobenzofuran)-3-(phenacylmethyl)imidazolium bromide

[0041]

[0042] The preparation process is as follows:

[0043] 1. Preparation of 5-formyl dihydrobenzofuran (2):

[0044] Under ice-water bath, slowly dropwise add phosphorus oxychloride (31.0ml, 0.333mol) into N,N-dimethylformamide (28.4ml, 0.366mol), react for 10 minutes, slowly dropwise add 2,3-di Hydrobenzofuran (1, 20.0g, 0.166mol), remove the ice-water bath, heat and stir at 85°C for 12 hours, pour the reaction system into ice water, add sodium hydroxide solution, adjust the pH value to 8-9, and use acetic acid Ethyl ether extraction, the organic phase washed with saturated brine, anhydrous Na 2 SO 4 After drying, filtering, and concentrating the solvent under reduced pressure, silica gel column chromatography (100-200 mesh) with petroleum ether-ethyl acetate (5:1) as the eluent was used to prepare 5-formyl dihydrobenzofuran ( 2, 22.8g), yield 93%;

[0045] The pre...

Embodiment 2

[0056] Example 21-(5-Methyl-substituted dihydrobenzofuran)-3-(4-methoxyphenacylmethyl)imidazolium bromide

[0057]

[0058] The preparation process is as follows:

[0059] 1. Preparation of 5-formyl dihydrobenzofuran (2): The method is the same as in Example 1.

[0060] 2. Preparation of 5-benzyl alcohol substituted dihydrobenzofuran (3): The method is the same as in Example 1.

[0061] 3. Preparation of 1-(5-methyl-substituted dihydrobenzofuran)imidazole (5a): The method is the same as in Example 1.

[0062] 4. Preparation of 1-(5-methyl-substituted dihydrobenzofuran)-3-(4-methoxyphenacyl)imidazolium bromide (7):

[0063] Dissolve 1-(5-methyl-substituted dihydrobenzofuran) imidazole (5a, 200mg, 1mmol) in toluene (20ml), add 4-methoxyphenacyl bromide (274mg, 1.2mmol) under stirring , the reaction was stirred and refluxed for 20 hours, cooled to room temperature, a solid precipitated out, filtered, the precipitate was washed several times with acetone, and dried to prepar...

Embodiment 3

[0069] Example 31-(5-Methyl-substituted dihydrobenzofuran)-3-(4-bromophenacylmethyl)imidazolium bromide salt

[0070]

[0071] The preparation process is as follows:

[0072] 1. Preparation of 5-formyl dihydrobenzofuran (2): The method is the same as in Example 1.

[0073] 2. Preparation of 5-benzyl alcohol substituted dihydrobenzofuran (3): The method is the same as in Example 1.

[0074] 3. Preparation of 1-(5-methyl-substituted dihydrobenzofuran)imidazole (5a): The method is the same as in Example 1.

[0075] 4. Preparation of 1-(5-methyl-substituted dihydrobenzofuran)-3-(4-bromophenacyl)imidazolium bromide (8):

[0076] 1-(5-Methyl-substituted dihydrobenzofuran) imidazole (5a, 200mg, 1mmol) was dissolved in toluene (20ml), and 4-bromophenacyl bromide (331mg, 1.2mmol) was added under stirring, and the reaction Stirred and refluxed for 24 hours, cooled to room temperature, a solid precipitated out, filtered, the precipitate was washed several times with acetone, dried,...

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Abstract

The invention discloses a 5-substituted dihydrobenzofuran-imidazolium salt compound and a preparation method thereof. The preparation method comprises the following steps of: performing Vilsmeier reaction by taking 2,3-dihydrobenzofuran as a raw material, thereby synthesizing 5-carboxaldehyde dihydrobenzofuran, reducing the 5-carboxaldehyde dihydrobenzofuran into 5-benzyl alcohol substituted dihydrobenzofuran in an alcohol by using sodiumborohydride, and then converting the 5-benzyl alcohol substituted dihydrobenzofuran into methanesulfonate, next, carrying out a reflux reaction between the methanesulfonate and imidazolium or benzimidazole in a solvent, thereby synthesizing 1-(substituted dihydrobenzofuran) imidazolium, and finally, on the basis, reacting the 1-(substituted dihydrobenzofuran) imidazolium with a halide to synthesize the 5-substituted dihydrobenzofuran-imidazolium salt compound. According to the invention, a pharmacophore with remarkable anti-tumor activity in a natural product is used as a precursor and then design and synthesis of anti-tumor medicine molecules are carried out, and consequently, the synthesized compound has excellent in-vitro anti-tumorous cytotoxin activity. Researches show that the compound has excellent in-vitro anti-cancer biological activity when the imidazolium structure unit is 5,6-dimethyl benzimidazole and the substituent group thereof on the site of 3 is 2-bromobenzyl, naphthoyl methyl or 4-bromophenacyl.

Description

technical field [0001] The invention relates to a 5-substituted dihydrobenzofuran-imidazolium salt compound, a preparation method thereof, and an anticancer application of a pharmaceutical composition in which the compound is an active ingredient. Background technique [0002] Cancer is a class of diseases that seriously threaten human health. The mainstay currently used to treat cancer is chemotherapy. Most of the chemotherapeutic drugs in clinical use have side effects such as nausea, vomiting, leukopenia, and bone marrow suppression. Therefore, finding highly active, non-toxic or low-toxic anticancer compounds has become an important topic in new drug research. Natural products and their related research are the source of pharmaceutical innovation. Search for physiologically active compounds from natural products, design and synthesize natural product-like libraries based on their molecular structure information, screen and discover lead compounds with high efficiency,...

Claims

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Application Information

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IPC IPC(8): C07D405/06A61K31/4184A61K31/4178A61P35/00
Inventor 张洪彬羊晓东李艳徐晓亮李莹超闫居明周宏宇
Owner YUNNAN UNIV
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