Novel triazolols antifungal compound, preparation method and application thereof

A triazole alcohol and compound technology, applied in the field of 1--2--3--2-alcohol compounds and their salts, can solve the problem of large side effects, narrow antibacterial spectrum, lack of antifungal drugs and anti-deep fungal drugs and other problems, to achieve strong antifungal, low toxicity, and wide antifungal spectrum effects

Inactive Publication Date: 2009-02-04
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as far as the antifungal drugs in clinical use are concerned, there are problems such as large side effects, narrow antibacterial spectrum, and easy drug resistance. Effective antifungal drugs, especially anti-deep fungal drugs, are very scarce, which is far from meeting the needs.

Method used

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  • Novel triazolols antifungal compound, preparation method and application thereof
  • Novel triazolols antifungal compound, preparation method and application thereof
  • Novel triazolols antifungal compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] The intermediate is synthesized according to the reaction scheme of a).

[0044] (1), preparation of 2-chloro-2', 4'-difluoroacetophenone

[0045] Put 200g (1.494mol) of anhydrous aluminum oxide and 150g (1.30mol) of m-difluorobenzene into a 1000mL three-necked bottle, stir at room temperature, slowly add 150g (1.30mol) of chloroacetyl chloride dropwise, and continue to Stir at room temperature for 30 minutes, slowly raise the temperature to 45°C, continue stirring at this temperature for 4.5 hours, pour the reaction solution into ice water as usual, precipitate solids, filter; the filtrate is extracted twice with 800 mL of dichloromethane, and combined Dichloromethane extract, washed with water until neutral, dried over anhydrous sodium sulfate, filtered, and the solvent was recovered to obtain a solid, which was combined twice and recrystallized with ethanol to obtain 2-chloro 2', 4'-difluoroacetophenone 215g, yield 88.2%, melting point: 46-47°C.

[0046] (2), prepa...

Embodiment 2

[0057] Example 2: Preparation of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[N-n-propyl-N-benzylamino ]-2-ol

[0058] Add 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(N-n-propylamino)- 0.55g (0.002mol) of 2-alcohol, 40mL of acetonitrile, 2g (0.019mol) of anhydrous sodium carbonate, 0.54g (0.003mol) of benzyl bromide, heated to reflux in an oil bath for 8 hours, then evaporated to dryness, extracted with 30mL of ethyl acetate, Filtration, ethyl acetate column chromatography (developing solvent chloroform:methanol (60:1), finally give 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-di Fluorophenyl)-3-[(N-n-propyl-N-benzylamino)-2-alcohol 600mg, yield 62.2%. (See compound 1 in Table 1 for specific spectral data)

Embodiment 3

[0059] Example 3: Preparation of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[N-n-propyl-N-(2- Fluorobenzyl)amino]-2-ol

[0060] Add 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(N-n-propylamino)- 0.8g (0.003mol) of 2-alcohol, 40mL of acetonitrile, 2g (0.019mol) of anhydrous sodium carbonate, 0.8g (0.0048mol) of o-fluorochlorobenzyl, heated to reflux in an oil bath for 8 hours, then evaporated to dryness, 30mL of ethyl acetate Extraction, filtration, ethyl acetate column chromatography (developer chloroform: methanol (80:1), finally 1-(1H-1,2,4-triazol-1-yl)-2-(2,4 -difluorophenyl)-3-[(N-n-propyl-N-(2-fluorobenzyl)amino)-2-alcohol 750mg, yield 59.6%. (Specific spectral data see compound 2 in Table 1 ) compound 3, 4 according to the above method.

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Abstract

The invention relates to the medical technical field, in particular to a new triazole alcohols antifungal compound and salts thereof with the following chemical structure formula and a preparation method and the application thereof; R1 is selected from n-propyl, isopropyl or butyl; R2 is selected from alkyl or halogen; the salts include hydrochloride, hydrobromide and methane sulphonate. The compound has strong antifungal activity on various fungi in shallow parts and deep parts. Compared with the antifungal medicines used in the existing clinical applications, the compound has the advantages of high efficiency, low toxicity, broad antifungal spectrum, and the like, and can be used for preparing new antifungal medicines.

Description

Technical field: [0001] The present invention relates to the technical field of medicine, in particular to a new class of imazazole antifungal compounds, i.e. 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluoro Phenyl)-3-(N-alkyl-N-substituted amino)-2-alcohol compounds and salts thereof, as well as their preparation methods and applications. Background technique: [0002] In recent years, with the extensive application of broad-spectrum antibiotics, antineoplastic drugs, and immunosuppressants, the widespread implementation of radiotherapy and organ transplantation, the widespread development of catheters and intubations, and the rapid increase in immunocompromised patients, especially AIDS patients, have resulted in Fungal infections, especially deep fungal infections, have risen sharply, and deep fungal infections have become the main cause of death from major diseases such as AIDS and tumors. However, as far as the antifungal drugs in clinical use are concerned, there are problem...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D249/08A61K31/4196A61P31/10
Inventor 吴秋业赵庆杰胡宏岗俞世冲姜远英邹燕柴晓云但志刚孙青䶮孙青
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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