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A novel azole antifungal compound and its preparation method and application

A technology of antifungal drugs and compounds, applied in antifungal agents, organic chemistry, etc., to achieve high yield, simple preparation method and good effect

Inactive Publication Date: 2016-04-06
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, no azole compound 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(1- Report on Substituted Benzyloxyethyl-1H-1,2,3 Triazol-4-yl)-2-ols

Method used

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  • A novel azole antifungal compound and its preparation method and application
  • A novel azole antifungal compound and its preparation method and application
  • A novel azole antifungal compound and its preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0035] R group and proton nuclear magnetic spectrum data of embodiment 1 part compound of the present invention

[0036] See Table 1 for the R groups and H NMR spectrum data of some compounds of the present invention.

[0037] Table 1 R group and proton nuclear magnetic spectrum data table of some compounds of the present invention

[0038] serial number

[0039] Note: The number in the R group in the table represents the position of substitution on the benzene ring.

Embodiment 2

[0040] The preparation of the intermediate of embodiment 2 compounds of the present invention

[0041] 1. Preparation of 2-chloro-2′,4′-difluoroacetophenone

[0042] Put 200g (1.494mol) of anhydrous aluminum trichloride and 150g (1.30mol) of m-difluorobenzene into a 1000mL three-necked bottle, stir at room temperature, and slowly add 150g (1.30mol) of chloroacetyl chloride dropwise. Continue to stir at room temperature for 30 minutes, slowly raise the temperature to 45°C, continue to stir at this temperature for 4.5 hours, pour the reaction solution into ice water as usual, precipitate a solid, and filter; the filtrate is extracted twice with 800 mL of dichloromethane, The dichloromethane extracts were combined, 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′-difluorophenethyl Ketone 215g, yield 88.2%, melting point...

Embodiment 3

[0051] Embodiment 3 Preparation of some compounds of the present invention

[0052] 1. Preparation of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[1-(2-fluorobenzyloxy)ethyl- 1H-1,2,3triazol-4-yl)]-2-ol (7a)

[0053] Take the compound 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[1-hydroxyethyl-1H- 1,2,3 Triazol-4-yl)]-2-ol 350 mg (1.0 mmol) in 20 mL dry CH 2 Cl 2 26mg (1.1mmol) of NaH was added slowly under the condition of ice bath, and after stirring for half an hour in the ice bath, 0.13mL (1.2mmol) of o-fluorobenzyl bromide was added, the reaction conditions remained unchanged, and the reaction was completed in about 2 hours. , add 20mL CH 2 Cl 2 Dilute, add a small amount of methanol slowly under ice bath to remove the remaining NaH, then wash with water and saturated brine, evaporate the solvent to dryness, and purify by column chromatography (developing solvent: ethyl acetate:petroleum ether=1:1) to obtain white Solid target compound 1-(1H-1,2,4-tria...

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Abstract

The invention provides a novel azole antifungal compound. According to the azole antifungal compound, a structural general formula is shown in the specification, wherein X is hydroxyl, Ar is 2,4-difluoro phenyl, and R is selected from hydrogen, alkyl, halogen, cyano-group, nitryl, amino or alkoxy and can be positioned at the ortho-position, meta-position or para-position of a benzene ring and can be mono-substituted or multi-substituted; the alkyl has 1 to 4 carbon atoms; the halogen is selected from F, Cl, Br and I; the amino is selected from -NH2, one or two aminos substituted by the alkyl and cyclic amino; and the alkoxy is selected from methoxyl, ethyoxyl and tert-butyl oxygroup. The invention also provides a method for preparing the compound and application of the compound to preparation of antifungal medicines. Compared with the conventional antifungal medicines which are applied clinically, the azole antifungal compound has the advantages of high antifungal activity on invasive fungi, high efficiency, low toxicity, broad spectrum and the like; and the method is simple and high in yield, and the prepared compound has a good antifungal effect.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical compounds, in particular to a novel azole antifungal compound and its preparation method and application. Background technique [0002] In recent years, with the widespread application of broad-spectrum antibiotics, antineoplastic drugs, and immunosuppressants, the widespread development of peritoneal dialysis, organ transplantation, and radiotherapy, and the rapid spread of immunodeficiency diseases, especially AIDS, Candida albicans, Cryptography neoformans The incidence of opportunistic deep fungal infections such as coccus and Aspergillus fumigatus has increased dramatically. Deep fungal infection has risen to the third largest infectious disease clinically, seriously threatening human life and health. Existing antifungal drugs are mainly allylamines that act on squalene epoxidase, azoles that act on lanosterol 14a-demethylase, and those that act on cell walls and -1,3-β-glucose Lipop...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/06A61K31/4196A61P31/10
Inventor 邹燕赵庆杰吴秋业廖俊汪亭胡宏岗俞世冲柴晓云黄生军
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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