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2-aryl-2,3-dihydro-4(1H)-quinolinone semicarbazone compound and application thereof

A technology of quinolinone and semicarbazide, applied in the field of medicine, can solve the problems of limited clinical application, obvious toxic and side effects, and lack of antifungal drugs

Active Publication Date: 2018-09-21
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, the morbidity and mortality of fungal infections have been increasing year by year, but clinically used antifungal drugs are relatively scarce, and azole antifungal drugs are still the first choice. Although these antifungal drugs have certain curative effects, but Because of its obvious toxic and side effects, and poor curative effect on deep fungal infections, its clinical application is limited

Method used

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  • 2-aryl-2,3-dihydro-4(1H)-quinolinone semicarbazone compound and application thereof
  • 2-aryl-2,3-dihydro-4(1H)-quinolinone semicarbazone compound and application thereof
  • 2-aryl-2,3-dihydro-4(1H)-quinolinone semicarbazone compound and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Preparation of 2-aminoacetophenone (A1)

[0056] Add 50ml of water, 50ml of ethanol, 8.00g (0.14mol) of reduced iron powder into a 250ml reaction bottle, and use NH 4 Adjust the pH of the solution to 4 with Cl, drop 2 drops of glacial acetic acid, heat up to 55°C for 1 hour, add 5.00 g (0.03 mol) of o-nitroacetophenone, heat up to 80°C, reflux for 3 hours, remove iron sludge by suction filtration while hot , the filtrate was extracted with dichloromethane (30ml × 3), the combined organic phases were washed with water until colorless and transparent, the organic phase was dried with anhydrous sodium sulfate, and the desiccant was filtered off and then concentrated under reduced pressure to obtain A1 as a light yellow transparent liquid. 3.44g, yield 84.11%, mp: 18℃~20℃, LC-MS(m / z): 134.2[M-H] - .

Embodiment 2

[0058] Preparation of 2-acetamidoacetophenone (B1)

[0059] Dissolve 4.05g (0.03mol) of 2-aminoacetophenone (A1) in 100ml of dichloromethane, then add 5.3ml (0.04mol) of triethylamine, and dropwise add 3.5ml (0.05 mol) acetyl chloride, after dropping, rise to room temperature and stir to react for 3h, add 100ml of ethyl acetate to dilute the reaction solution, separate the organic phase, and wash with water until the organic layer is colorless, then wash once with 30ml of saturated saline, and wash the organic phase with Dry over magnesium sulfate, filter out the desiccant, and concentrate under reduced pressure to obtain B1 as a white solid, with a yield of 4.50 g and a yield of 84.7%, mp: 80°C to 82°C, LC-MS (m / z): 176.8 [M-H ] - .

[0060] Preparation of 2-acetamido-4-chloroacetophenone (B2)

[0061] Using 2-amino-4-chloroacetophenone as the raw material, 2-acetamido-5-chloroacetophenone (B2) was prepared according to the preparation method of B1, off-white solid, yield ...

Embodiment 3

[0067] Preparation of (E)-N-[2-(3-phenylacryloyl)phenyl]acetamide (C1)

[0068] Dissolve 5.31g (0.03mol) of 2-acetamidoacetophenone (B1) in 100ml of methanol, then add 3.18g (0.03mol) of benzaldehyde, and add 30ml of 5% sodium hydroxide solution dropwise under ice-cooling. After completion, reacted at 0°C for 8 hours, poured the reaction solution into 250ml of ice water, a large amount of light yellow solid was precipitated, filtered with suction, washed the filter cake with water, and dried to obtain C1 as a light yellow solid. The yield was 5.09g, the yield was 64.4%, mp : 159°C~161°C, LC-MS (m / z): 265.31.

[0069] Using intermediates B1-B4 as raw materials, refer to the preparation method of C1, and react with various aromatic aldehydes to prepare intermediates C2-C34. The results are shown in Table 1.

[0070]

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Abstract

The invention relates to the field of medicine technology, and a series of novel 2-aryl-2,3-dihydrogen-4(1H)-quinolinone semicarbazone derivatives (I) and pharmaceutically acceptable salts, solvates,optical isomers or polymorphs are designed and synthesized. The derivative (I) and its pharmaceutically acceptable salt, solvate, optical isomer or polymorph can be mixed as an active ingredient witha pharmaceutically acceptable carrier to prepare a pharmaceutical composition. A double dilution method is used for test of the antifungal activity of the derivative (I) and its pharmaceutically acceptable salt, solvate, optical isomer or polymorph, and the results show that the derivative has stronger killing effect on clinically common pathogenic fungi, and is expected to overcome the defects oflarge toxic and side effects, easy generation of drug resistance of azole antifungal medicines which are widely used clinically. The specific formula is shown in the description.

Description

technical field [0001] The invention relates to the technical field of medicine, specifically, it is 2-aryl-2,3-dihydro-4(1H)-quinolinone semicarbazone derivatives with antifungal activity and pharmaceutically acceptable Salts, solvates, optical isomers or polymorphs and uses thereof. Background technique [0002] Mycosis is a multiple, refractory disease. In recent years, the morbidity and mortality of fungal infections have been increasing year by year, but clinically used antifungal drugs are relatively scarce, and azole antifungal drugs are still the first choice. Although these antifungal drugs have certain curative effects, but Because of its obvious toxic and side effects, and its poor curative effect on deep fungal infections, its clinical application is limited. Therefore, it is still a very meaningful work to develop antifungal drugs with high efficiency, low toxicity, new mechanism of action and novel structure. [0003] Natural flavonoids (dihydroflavones) are...

Claims

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Application Information

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IPC IPC(8): C07D215/42C07D409/04C07D405/04A61K31/47A61K31/4709A61P31/10
CPCA61P31/10C07D215/42C07D405/04C07D409/04
Inventor 郭春苏昕候壮宋少杰杨晓光徐航安然刘小倩韩长宏
Owner SHENYANG PHARMA UNIVERSITY
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