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Azole derivatives, preparation method and application thereof

A triazole and compound technology, applied in the field of compounds with antifungal activity, can solve problems such as side effects, bone marrow suppression, and complicated treatment of deep fungal infections

Inactive Publication Date: 2010-08-11
TIANJIN INSTITUTE OF PHARMA RESEARCH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the interaction between drugs makes the treatment of deep fungal infections more complicated. Therefore, there is an urgent clinical need for new deep antifungal drugs with high efficiency, low toxicity, wide antibacterial spectrum and high selectivity.
[0006] Linezolid is a new type of oxazolidinone antibacterial drug. Its antibacterial spectrum includes Gram-positive bacteria and anaerobic bacteria. It has a strong inhibitory effect on multidrug-resistant Gram-positive bacteria. Gram-negative bacteria are ineffective
In addition, linezolid can cause myelosuppression, thrombocytopenia and other side effects after prolonged use

Method used

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  • Azole derivatives, preparation method and application thereof
  • Azole derivatives, preparation method and application thereof
  • Azole derivatives, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0049] Preparation of intermediate (1-1)

[0050]

[0051] Add 17.5g (0.1mol) of 5-bromo-2-furfural to the reaction flask equipped with stirring, condenser and thermometer, then add 50mL of absolute ethanol, add 10.4g (0.15mol) of hydroxylamine hydrochloride and distilled water dropwise under stirring 3mL, and then add 10mL of 50% (m / m) sodium hydroxide solution, and keep the reaction at 25°C for about 5h (the plate layer shows that the reaction is complete). Stop the reaction, pour the reaction solution into 200 mL of ice water, and let it stand overnight. A white solid precipitated out and was filtered to obtain a crystalline product (HPLC: 99.1%). Rf = 0.48 [single point, developer: v (ethyl acetate): v (petroleum ether) = 3: 1, add appropriate amount of triethylamine].

[0052] With reference to the method of Reference Example 1, those skilled in the art can easily prepare the intermediate ( 1 )-2~intermediate ( 1 )-4.

[0053]

Embodiment 2

[0055] Intermediate ( 2 )-1 preparation

[0056]

[0057] Add 19.0g (0.1mol) intermediate ( 1 )-1, then add 150mL of dichloromethane, add bromosuccinimide (NBS) 19.5g in batches under stirring, react at room temperature for about 4h, and then continue to reflux for 1h (the plate layer shows that the reaction is complete). Stop the reaction, pour the reaction solution into 80 mL of ice water, separate the dichloromethane layer, wash with water three times, and dry. The solvent was distilled off under reduced pressure to obtain a white solid product (HPLC: 98.3%). Rf = 0.50 [single point, developer: v (ethyl acetate): v (petroleum ether) = 3: 1, add appropriate amount of triethylamine].

[0058] Referring to the method of Reference Example 2, those skilled in the art can easily prepare the intermediate ( 2 )-2~intermediate ( 2 )-4.

[0059]

[0060]

Embodiment 3

[0062] Intermediate ( 3 )-1 preparation

[0063]

[0064] Add 26.9g (0.1mol) intermediate ( 2 )-1, then add 100mL of dichloromethane, cool in an ice-water bath, and add 20mL of triethylamine. 6.7 g (0.12 mol) of propynyl alcohol was added dropwise with stirring, and reacted at 0° C. for about 4 hours, then warmed up to room temperature and reacted for 18 hours (the plate showed that the reaction was complete). The reaction was stopped, and the reaction solution was washed 3 times with saturated brine and dried. The solvent was distilled off under reduced pressure to obtain a light yellow solid product, which was recrystallized from absolute ethanol (HPLC: 98.1%). Rf = 0.35 [single point, developer: v (ethanol): v (petroleum ether) = 1: 4].

[0065] With reference to the method of Reference Example 3, those skilled in the art can easily prepare the intermediate ( 3 )-2~intermediate ( 3 )-4.

[0066]

[0067] Reference Example 4:

[0068] Intermediate ( 4 )-1 pr...

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Abstract

The invention belongs to the technical field of antifungal medicaments, and provides azole derivatives with a structure of a general formula (I) and pharmaceutically acceptable salts thereof, wherein definitions of A, B, Y and R are as described in instructions. The invention also relates to a preparation method for the compounds, and also discloses medicinal compositions taking the compounds and the pharmaceutically acceptable salts thereof as active ingredients, as well as application thereof in the aspect of acting as antifungal medicaments.

Description

technical field [0001] The invention belongs to the technical field of medicine, more specifically, relates to a class of compounds with antifungal activity, its preparation method, composition and application. Background technique [0002] Fungal infections can be divided into superficial and deep types according to the different parts of their invasion. Superficial fungal infection is a common and frequently-occurring disease, mostly seen on the skin and nails; deep fungal infections are more common Candida albicans and Cryptococcus neoformans, although the incidence rate is low but the harm is greater, and severe infection can be life-threatening. Especially in recent decades, with the widespread use of broad-spectrum antibiotics, corticosteroids, antineoplastic drugs and immunosuppressants, the widespread implementation of radiotherapy and organ transplantation, the widespread development of catheters and intubations, and the widespread use of immunocompromised patients ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D413/14A61K31/422A61P31/10A61P31/04
Inventor 刘登科刘颖黄长江刘默刘冰妮陈继方吴疆邹美香
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH