Unlock instant, AI-driven research and patent intelligence for your innovation.

Vancomycin derivatives, preparation method and medicinal use thereof

A technology of derivatives and uses, applied in the field of medicine, can solve problems such as high toxicity

Inactive Publication Date: 2017-07-11
FUDAN UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Especially in the last decade, the emergence of highly virulent vancomycin-resistant Staphylococcus aureus (VRSA) has brought new major challenges to the treatment of infectious diseases caused by drug-resistant bacteria.

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
  • Vancomycin derivatives, preparation method and medicinal use thereof
  • Vancomycin derivatives, preparation method and medicinal use thereof
  • Vancomycin derivatives, preparation method and medicinal use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Synthesis of Nitrogen Heterocyclic Amino Substituted Vancomycin

[0058]

[0059] As shown in Scheme 2, take a 10ml reaction tube, add vancomycin hydrochloride (80mg, 0.054mmol), dissolve it with 0.8ml dry DMF, add (2) (R 4 =nC 10 h 21 , n=2) 26 mg (0.108 mmol). DIEA (37μl, 28mg, 0.216mmol) was added dropwise, protected by Ar, and reacted at room temperature for 31h. Then add NaCNBH320mg (0.324mmol), add 0.8ml of methanol to dissolve, add dropwise TFA25μl (37mg, 0.324mmol), and react at room temperature for 15h. Remove the methanol in the reaction solution by distillation under reduced pressure, add 50ml of ether, a white solid precipitates out, suck off the supernatant, wash the residue with ether 30ml*2, after drying, dissolve the sample with methanol: water = 1:4, RP- 18 silica gel column layer, CH3OH:H2O=1:4→1:1 elution, to obtain powdery solid (3)a19mg, yield 20%. 1H NMR(DMSO-d6)δ7.53-7.39(m,7H),7.32-7.08(m,9H),3.82(s,1H),1.28(s,3H),1.05(d,J=6.0Hz, 3H),0.9...

Embodiment 2

[0064] The final product (3) a-h was tested for in vitro antibacterial activity against Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, methicillin-resistant Staphylococcus aureus 09-250, and vancomycin-resistant Enterococcus 193, 186, 435 . Methods According to the 2006 CLSI (Clinical Laboratory Standards Institute) recommended agar two-fold dilution method for the determination of the minimum inhibitory concentration of antibacterial drugs (Minimal Inhibitory concentration MIC). Experimental design: Take 1ml of antibacterial drugs of different types and concentrations and pour them into a 9cm sterile empty plate, then immediately pour 19ml of sterile M-H agar cooled to about 55°C on the plate, mix well with the drug solution, and make the culture The final concentration of base antibacterial drugs was 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25, 0.125, 0.06 μg / ml; meanwhile, M-H plate without antibacterial drugs was prepared as a control. Bacterial inoculation ...

Embodiment 3

[0067] Embodiment 3 in vivo antibacterial protection test

[0068] 1) Test strain

[0069] Clinical isolate: methicillin-resistant Staphylococcus aureus 11002.

[0070] 2) Experimental animal system:

[0071] Animal level: clean level.

[0072] Gender and number: 300 KM mice in total, 150 males and 50 males.

[0073] Animal weight: body weight 18-22g.

[0074] Source of experimental animals: Shanghai Slayke Experimental Animal Center, Chinese Academy of Sciences, license number SCXK (Shanghai) 2011-0005.

[0075] Animal feeding and management: SPF-level environmental animal room, experimental animal use license number: SYXK (Shanghai) 2009-0068.

[0076] Feeding of animals: All animals were fed with standard sterilized full-price mouse feed, drinking water for animals was supplied by drinking bottles, and animals drank water freely. Animal feeding: 10 animals were raised in each cage before modeling, and 5 animals / cage were raised after modeling. Animals were set at a r...

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

Vancomycin derivatives and their preparation methods and medicinal uses. The present invention belongs to the field of medical technology, and relates to nitrogen-heterocyclic substituted glycopeptide antibiotic derivatives of general formula (1), their pharmaceutically acceptable salts, their isomers, the preparation methods of these compounds, and these compounds Use in the preparation of medicines for treating or preventing bacterial infectious diseases. In vitro antibacterial experiments show that the compound of the present invention has higher antibacterial activity (>60 times) than vancomycin or norvancomycin, especially the antibacterial activity against a variety of Gram-positive bacteria is significantly higher for vancomycin and norvancomycin. Therefore, it can be used to prepare medicines containing the derivatives as active ingredients, especially medicines for antibacterial infection.

Description

technical field [0001] The present invention belongs to the technical field of medicine, and specifically relates to nitrogen-heterocyclic substituted glycopeptide antibiotic derivatives, pharmaceutically acceptable salts, isomers thereof, preparation methods of these compounds, and the use of these compounds in the preparation of therapeutic Or use in medicines for preventing bacterial infectious diseases. Background technique [0002] According to reports, glycopeptide antibiotics are a class of antibiotics with very complex structures that are effective against Gram-positive drug-resistant bacteria. These antibiotics, which are widely used in clinical practice, include vancomycin, norvancomycin, and teicoplanin. Ning et al. They all have a similar heptapeptide oxygen-linked cup-shaped rigid framework system and special amino sugar substituents in structure. Among them, vancomycin, as a representative and most widely used natural glycopeptide antibiotic, was isolated fro...

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): C07K9/00A61K38/14A61P31/04
Inventor 孙逊徐亮金潇昌军江永伟
Owner FUDAN UNIV