Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Furanone-aryl-oxazolidinone type compound and its preparation method and use

A technology of oxazolidinone and furanone, which is applied in the application field of preparing antibacterial drugs, can solve the problems that there are no dual-target antibacterial compounds, and achieve good inhibition and killing effects and high antibacterial activity

Active Publication Date: 2015-08-05
南京淘普生物技术有限公司
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Based on this idea, the present invention uses the principle of skeleton transition and the method of computer-aided drug design to design and synthesize a furanone- Oxazolidinone-type multi-target antibacterial drugs, they block the most critical process in bacterial life activities - protein synthesis from different ways, and there is no dual target targeting TyrRS and S30 ribosomal subunit Antimicrobial Compounds Emerge

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Furanone-aryl-oxazolidinone type compound and its preparation method and use
  • Furanone-aryl-oxazolidinone type compound and its preparation method and use
  • Furanone-aryl-oxazolidinone type compound and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: (S)-3-(4-(4-(3-(3-methoxyphenyl)-2(5H)-furanone-4-yloxyethyl)piperazin-1-yl )-3-hydroxyphenyl)-5-benzamidomethyl-2-oxazolidinone (29)

[0027] Step 1: Dissolve 1.88g (10mmol) sodium 3-methoxyphenylacetate in 15mL DMSO, add 1.2mL ethyl bromoacetate at room temperature, raise the temperature to 35°C and react for 8h, after the reaction is complete, dilute with ethyl acetate and wash with water , the organic layer was washed with saturated brine until neutral, dried, concentrated, and subjected to silica gel column chromatography, the eluent was petroleum ether-AcOEt, and the volume ratio of petroleum ether to AcOEt was 4:1 to obtain 2.2g oily 2-(3 -ethyl methoxyphenylacetoxy)acetate;

[0028] Step 2: Dissolve 2.01 g of ethyl 2-(3-methoxyphenylacetoxy) acetate in a constant pressure funnel containing 10 mL of anhydrous THF, and add 0.19 g of NaH into a flask containing 5 mL of anhydrous THF 2-(3-methoxyphenylacetoxy) ethyl acetate solution in THF was slowly ad...

Embodiment 2

[0042] Embodiment 2: the antibacterial activity of compound

[0043] Bacteria were suspended in MH medium at a concentration of approximately 10 5 cfu. mL -1 , add the bacterial solution to a 96-well plate (100 μL of bacterial solution per well), use the culture medium as a blank control, use DMSO instead of a test substance as a negative control, use penicillin G as a positive control for Gram-positive bacteria, and use penicillin G as a positive control for Gram-positive bacteria. Kanamycin was used as a positive control for Shi-negative bacteria, and ketoconazole was used as a positive control for fungi. Dissolve the test substance in DMSO to prepare 1600, 800, 400, 200, 100, 50 μg. mL -1 solution (for MIC 50 Less than 5μg. mL -1 Yes, when carrying out one-step experiment, the prepared concentration gradient is 100, 50, 25, 12.5, 6.25μg. mL -1 ), was added to a 96-well plate at an amount of 11 μL per well, and four parallel experiments were performed for each conce...

Embodiment 3

[0046] Example 3: Activity of ribosomal protein synthesis

[0047] Take the Escherichia coli liquid in the logarithmic growth phase, centrifuge and wash the cells twice with 5mL buffer solution at 3°C. The composition of the buffer solution is as follows: 0.01M Tris (pH7.8), 0.017M magnesium acetate and 0.06M potassium chloride. The resulting cells were frozen at -70°C, and after thawing, they were ground for 15 minutes with aluminum oxide twice the wet weight of the cells to obtain a crude extract of S30 ribosomes. Dissolve the crude extract of S30 ribosomes in 0.25mL of 0.017M magnesium acetate buffer, add a certain concentration of the test compound, incubate at room temperature for 15min, and then add primer polyuridine, 4×10 -9 mol[ 14 C] phenylalanine, 5 × 10 -9 mol of phenylalanine and 5 x 10 -9 mol of other essential amino acids, continue to incubate for 15 min. The synthesized protein was precipitated by adding 1 mL of 10% trichloroacetic acid solution at 3 °C, f...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a furanone-aryl-oxazolidinone type compound which is characterized by comprising the structural formula as shown in the specification. The furanone-aryl-oxazolidinone type compound has a good inhibiting effect on staphylococcus epidermidis, klebsiella pneumoniae, cryptococcus neoformans and the like, can be used for preparing anti-infective medicaments for treating intestinal infection, pneumonia, suppuration wound and the like. The invention further discloses a preparation method of the furanone-aryl-oxazolidinone type compound.

Description

technical field [0001] The invention relates to a preparation method of a class of furanone-aryl-oxazolidinone compounds and their application in the preparation of antibacterial drugs. technical background [0002] The rapid spread of drug-resistant bacteria makes the treatment of bacterial infections more and more difficult. Clinical studies have shown that bacterial resistance poses a threat to almost all antimicrobials, extended-spectrum beta-lactams produced by Gram-negative bacilli such as Klebsiella pneumoniae and Escherichia coli in the late 1980s and 1990s Enzymes (ESBLs) and inducible β-lactamases (AmpC enzymes) can hydrolyze most β-lactamases including oxyiminos (cefetazidime, ceftriaxone, cefotaxime, aztreonam, etc.) - Lactam antimicrobials. Most strains producing ESBLs are multi-drug resistant strains, which are also resistant to fluoroquinolones. According to relevant reports, fluoroquinolones have different degrees of drug resistance to Enterococcus, Klebsi...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D413/12C07D413/14A61K31/497A61K31/5377A61K31/422A61K31/4439A61P31/04
CPCC07D413/12C07D413/14
Inventor 肖竹平胡桐芳王金祥
Owner 南京淘普生物技术有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com