Novel ketolide compound and preparation method and application thereof

A compound and ketolide technology, which is applied in the field of telithromycin ketolide-like compounds with aromatic ring-linked tetrazolylidines as side chains and the preparation thereof, can solve problems such as rising, and achieve strong activity and major industrialization prospects , the effect of novel structure

Inactive Publication Date: 2010-08-04
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the abuse of antibiotics and antibacterial drugs, the drug resistance of bacteria has increased rapidly. In recent years, the drug resistance of erythromycin to pneumococcus has increased from 5% to 40%, and the proportion of cross-resistance to penicillin is also increasing

Method used

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  • Novel ketolide compound and preparation method and application thereof
  • Novel ketolide compound and preparation method and application thereof
  • Novel ketolide compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Preparation of Aromatic Tetrazoles

[0041] method one:

[0042] Add cyanopyridine (1,1 mmol) into a three-necked flask and dissolve it in N,N-dimethylformamide (1.25mL), add sodium azide (3equiv) and ammonium chloride (3equiv) in sequence under stirring ; Under nitrogen protection, react at 130°C in an oil bath for 22h; cool to room temperature, add saturated sodium bicarbonate solution (2.5mL) and ethyl acetate (2.5mL) to the reaction solution, shake, transfer to a separatory funnel, and separate The organic layer; the solution layer was slowly acidified with concentrated hydrochloric acid to pH 4-5, stirred and left to stand, and crystals were precipitated; suction filtered, the mother liquor was cooled in ice water, and crystals continued to be precipitated, and the above crystals were combined, and an appropriate amount of The product was washed with distilled water to obtain the product. When the aryl nitrile is 2-cyanopyridine, the product 3a is obtained; when ...

Embodiment 2

[0052] The product 3 (1 mmol) obtained in Example 1 was dissolved in N,N-dimethylformamide (5 mL), and potassium carbonate (1 mmol) and N-bromoalkylphthalimide (1 mmol) were added in sequence; Under the protection of nitrogen, react at 80°C for 10h. After the reaction is complete, pour the reaction solution into 10 mL of ice water, filter, wash the filter cake with a small amount of ice water, and use petroleum ether: ethyl acetate = 1:1 to petroleum ether: ethyl acetate: dichloromethane = 1:1: 1 is developing agent silica gel (200-300 order) column chromatography, obtains the product. Depending on the starting material 3, different products 4a-4q can be obtained.

[0053] 4a: 2-[3-(5-(Pyridin-2-yl)-1H-tetrazol-1-yl)propyl)]-isoindole-1,3-2H-dione, white solid, yield rate 35%, 1 H NMR (300MHz, CDCl 3 ): δ8.83(m, 3H), 8.33(d, J=7.8Hz, 1H), 7.83(m, 1H), 7.72(m, 2H), 7.35(m, 2H), 5.03(t, J= 7.8Hz, 2H), 3.83(t, J=6.9Hz, 2H), 2.39(m, 2H); 13 C NMR (CDCl 3 ): δ168.1, 151.5, 1...

Embodiment 3

[0071]Dissolve the product 4 (1 mmol) obtained in Example 2 in a mixture of absolute ethanol (7 mL) and acetonitrile (5 mL), add hydrazine monohydrate (2 equiv), and heat to reflux for 6 h; after the reaction is complete, cool to room temperature; Filter the reaction solution, wash the filter cake with a small amount of 95% ethanol, remove the solvent in the filtrate by rotary evaporation, add sodium hydroxide solution (2mol / L, 10mL) to the residue; add dichloromethane (10mL×3) for extraction, and combine the organic phases , washed with saturated brine, and dried over anhydrous sodium sulfate. Filtrate, concentrate, and use dichloromethane:methanol:triethylamine=9:1:0.1 as the developing solvent for silica gel (200-300 mesh) column chromatography to obtain the aromatic ring tetrazolidinyl amine product. According to the different raw materials 4a-4q, the products 5a-5q can be correspondingly obtained respectively.

[0072] 5a: 3-[5-(pyridin-2-yl)-1H-tetrazol-1-yl]propylamine...

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Abstract

The invention discloses a ketolide compound similar with the telithromycin antibiotic. The compound has a structural formula as the accompanying drawing. The compound of the invention belongs to a third generation erythromycin analogue antibiotic, has novel structure and stronger activity than the macrolide antibiotic used clinically, has good antibacterial activity on the drug-resistance bacteria by the primary research and has great industrialization prospect.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a novel macrolide antibiotic ketolide compound and its preparation method and application, specifically, a thalyl-like compound with an aromatic ring tetrazolidinyl as a side chain Mycin ketolide compound and its preparation method and application. Background technique [0002] Bacterial infections threaten the survival of humans. Antibiotics are clinically commonly used drugs for infectious diseases, and their demand is huge. However, due to the non-standard use of antibiotics in clinical practice, the problem of bacterial resistance has been caused. In recent years, more and more bacteria have developed resistance to antibiotics, even multi-drug resistance. Bacterial infection has become more and more difficult to deal with, and has become one of the serious problems facing the cause of human health. Methicillin-resistant Staphylococcus aureus (MRSA) was first discovered...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/00C07H1/00A61K31/7056A61K31/706A61P31/04
Inventor 陈卫民宋秋玲张文郭葆秦
Owner JINAN UNIVERSITY
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