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

Nitrogen-heterocycle-containing artemisinin derivative and preparation method thereof

A technology of artemisinin derivatives and nitrogen heterocycles, applied in the field of medicine, can solve the problems of increased sensitivity and weak anti-Escherichia coli activity, and achieve the effects of enhanced sensitivity and strong synergistic antibacterial effect.

Inactive Publication Date: 2016-04-20
ARMY MEDICAL UNIV
View PDF4 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, artesunate can increase the sensitivity of Escherichia coli to antibiotics such as gentamicin, and its target may be related to the efflux pump protein AcrB, but the antibacterial activity of artesunate, especially against Escherichia coli The activity of bacteria is not strong

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
  • Nitrogen-heterocycle-containing artemisinin derivative and preparation method thereof
  • Nitrogen-heterocycle-containing artemisinin derivative and preparation method thereof
  • Nitrogen-heterocycle-containing artemisinin derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 112

[0046] Example 112 Synthesis of β-(2-bromoethoxy) dihydroartemisinin (B)

[0047]

[0048] Add 11.4g (40mmol) of dihydroartemisinin, 2.9ml (40mmol) of 2-bromoethanol and 250ml of THF into a 500ml round bottom flask, add 8ml of BF3.Et2O under the protection of argon, and place it in an ice bath to stir for 6h . The reaction progress was monitored by TLC (EtOAc:PE=1:4). After the reaction was completed, a saturated NaHCO3 solution was added. After separation, the organic layer was collected, the aqueous layer was separated by extraction with EtOAc (60ml×2), and the organic layers were combined. The organic layer was washed with 50 ml of saturated saline solution, then dried over anhydrous MgSO4, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was recrystallized in a mixed solvent of petroleum ether and ethyl acetate, filtered and vacuum-dried to obtain 13.1 g of white crystals with a yield of 83.7%.

[0049] MS (ESI, m...

Embodiment 2

[0050] Example 2 Synthesis of DHA25. The synthetic route of 12β-(2-(4-amino-1H-imidazol-1 base)ethoxy)dihydroartemisinin (named DHA25) is as follows:

[0051]

[0052] 1.17g (3mmol) intermediate, 0.41g (3mmol) K 2 CO 3 , 0.049g (0.3mmol) KI and 0.4g (4mmol) 4-amino-1H-imidazole were added to a 100mL round bottom flask. 50mLCH 3 CN was dissolved, and the mixture was reacted at 50° C. for 36 h; the reaction process was monitored by TLC (EtOAc:PE=1:3). After the reaction was completed, 15 mL of dichloromethane and 20 mL of saturated NaCl solution were added. After separation, the organic layer was collected, and the aqueous layer was separated with dichloromethane (10 mL×2) extract, and then the organic layers were combined. The organic layer was washed with 20 mL of saturated brine solution, then washed with anhydrous Na 2 SO 4 Drying; the solvent was removed by distillation under reduced pressure to obtain a crude product. After passing the crude product through the ...

Embodiment 3

[0054] Example 3 Synthesis of DHA26. The synthetic route of 12β-(2-(4-nitro-1H-imidazol-1 base)ethoxy)dihydroartemisinin (named DHA26) is as follows:

[0055]

[0056] 1.22g (3mmol) intermediate, 0.41g (3mmol) K 2 CO 3 , 0.049g (0.3mmol) KI and 0.45g (4mmol) 4-nitro-1H-imidazole were added to a 100mL round bottom flask. 50mLCH 3 CN was dissolved, and the mixture was reacted at 50° C. for 36 h; the reaction process was monitored by TLC (EtOAc:PE=1:3). After the reaction was completed, 15 mL of dichloromethane and 20 mL of saturated NaCl solution were added. After separation, the organic layer was collected, and the aqueous layer was separated with dichloromethane (10 mL×2) extract, and then the organic layers were combined. The organic layer was washed with 20 mL of saturated brine solution, then washed with anhydrous Na 2 SO 4 Drying; the solvent was removed by distillation under reduced pressure to obtain a crude product. After passing the crude product through the...

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 present invention discloses a nitrogen-heterocycle-containing artemisinin derivative and a preparation method thereof, the derivative is a compound of a formula I, and X is imidazolyl, thiazolyl, oxazolyl or thiazolidinyl. The present invention also discloses use of the derivative in resisting Escherichia coli infection, and especially, the derivative shows a very strong synergistic antibacterial effect on Escherichia coli by combination with an artemisinin drug.

Description

technical field [0001] The invention belongs to the field of medicine, and specifically relates to a nitrogen-containing heterocyclic artemisinin derivative and its preparation and application, especially the application for treating Escherichia coli infection. Background technique [0002] With the widespread use of antibacterial drugs, bacterial resistance to drugs is increasing. Gram-negative bacteria are the most common clinical pathogens, and their drug resistance is increasing. Among them, the detection rate of Escherichia coli and Pseudomonas aeruginosa is as high as 60%-81%. [0003] At present, the drug resistance mechanisms of bacteria mainly include the following: (1) production of inactivating enzymes; (2) changes in the target of antibacterial drugs; (3) changes in metabolic pathways; (4) reduced drug accumulation, including active efflux mechanisms (efflux pump) enhancement and decreased permeability of the bacterial outer membrane. For the special bacterial ...

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
IPC IPC(8): C07D493/20A61K31/427A61K31/422A61K31/4178A61K31/454A61P31/04
CPCC07D493/20Y02A50/30
Inventor 周红宋羿覃容欣潘夕春郑江
Owner ARMY MEDICAL UNIV
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