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

A kind of artemisinin derivative, its synthesis and application

A derivative, artemisinin technology, applied in the field of drug synthesis, can solve the problems of no effective treatment method, difficulty in producing specific vaccines, human health threats, etc., and achieves simple and easy preparation method, good reproducibility, and environmental pollution. small effect

Active Publication Date: 2019-09-03
贝克诺顿(浙江)制药有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the extremely rapid mutation of HIV, it is difficult to produce a specific vaccine, and there is no effective treatment so far, which poses a great threat to human health

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
  • A kind of artemisinin derivative, its synthesis and application
  • A kind of artemisinin derivative, its synthesis and application
  • A kind of artemisinin derivative, its synthesis and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Embodiment 1: Preparation of KPC-4000055

[0045]

[0046] Dissolve dihydroartemisinin (300mg, 1.06mmol, 1.0eq) and n-octanol (331mmL, 2.11mmol, 2.0eq) in a 10mL three-necked flask filled with 5mL of dichloromethane, replace nitrogen, and cool to -10 Add boron trifluoride diethyl ether (53mmL, 422μmol, 0.4eq) dropwise at °C and stir at this temperature for 2h. TLC (ethyl acetate:petroleum ether=2:8) showed that the reaction was complete. The reaction solution was slowly poured into water to quench, extracted 3 times with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed on a rotary evaporator to obtain a crude product, which was passed through the column layer Purification by analysis (ethyl acetate:petroleum ether=2:8) gave colorless oily liquid KPC-4000055 (320 mg, yield 76%).

[0047] KPC-4000055: 1 H NMR (800MHz, CHLOROFORM-d) δ: 5.39(s, 1H), 4.78(d, J=3.3Hz,...

Embodiment 2

[0050] Embodiment 2: Preparation of KPC-4000056

[0051]

[0052] Dihydroartemisinin (1.0g, 3.52mmol, 1.0eq) and 1,4-butanediol (3.11mL, 35.17mmol, 10.0eq) were dissolved in a 25mL three-necked flask containing 10mL of dichloromethane, Nitrogen was replaced, the temperature was lowered to 5°C, and boron trifluoride diethyl ether (442mmL, 3.52mmol, 1.0eq) was added dropwise, and stirred at this temperature for 2h. TLC (ethyl acetate:petroleum ether=4:6) showed that the reaction was complete. The reaction solution was slowly poured into water to quench, extracted 3 times with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed on a rotary evaporator to obtain a crude product, which was passed through the column layer Purification by analysis (ethyl acetate:petroleum ether=4:6) gave white solid KPC-4000056 (1.1 g, yield 88%).

[0053] KPC-4000056: 1 H NMR (800MHz, CHLOROFORM...

Embodiment 3

[0056] Embodiment 3: Preparation of KPC-4000057

[0057]

[0058] Dissolve dihydroartemisinin (399mg, 1.40mmol, 1.0eq) and KPC-4000056 (500mg, 1.40mmol, 1.0eq) in a 25mL three-neck flask filled with 10mL of dichloromethane, replace nitrogen, and cool down to - Boron trifluoride diethyl ether (178mmL, 1.40mmol, 1.0eq) was added dropwise at 20°C and stirred at this temperature for 2h. TLC (ethyl acetate:petroleum ether=4:6) showed that the reaction was complete. The reaction solution was slowly poured into water to quench, extracted 3 times with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed on a rotary evaporator to obtain a crude product, which was passed through the column layer Purification by analysis (ethyl acetate:petroleum ether=4:6) gave white solid KPC-4000057 (650 mg, yield 76%).

[0059] KPC-4000057: 1H NMR (800MHz, CHLOROFORM-d) δ: 5.38(s, 1H), 5.33(s, 1H)...

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 belongs to the field of drug synthesis, particularly discloses an artemisinin derivative as well as a preparation method and an application, and more particularly discloses an artemisinin derivative as well as a preparation method and an application thereof in anti-tumor drugs and anti-HIV drugs. The artemisinin derivative disclosed by the invention has a structure as shown in a formula I, wherein R is a residual radical of other compounds. The preparation method of the artemisinin derivative as shown in the formula I is simple and feasible, good in repeatability and small in environmental pollution, and can be used for massively preparing the compound as shown in the formula I. The compound as shown in the formula I has obvious anti-tumor activity and anti-HIV activity.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to an artemisinin derivative, its synthesis and application. Background technique [0002] Artemisia annua, also known as Artemisia annua L, is an annual herb belonging to the family Asteraceae. Artemisinin is a sesquiterpene lactoid antimalarial drug extracted from the traditional Chinese medicine Artemisia annua by Chinese pharmaceutical workers in the early 1970s. Based on this structure, a series of antimalarial actives have been synthesized and semi-synthesized successively. Derivatives of dihydroartemisinin, artesunate, artemether, artether, etc. [0003] The antimalarial activity of artemisinin and its derivatives has been recognized worldwide, and has the advantages of rapid onset of action, high efficacy, and low toxicity and side effects. In addition to being widely used in antimalarial treatment, artemisinin drugs also have various other pharmacological effects...

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): C07D493/18C07D493/20C07D519/00C07H15/26C07H1/00A61K31/357A61K31/7048A61P31/18A61P35/00A61P35/02
Inventor 李剑峰坝德伟杨兆祥
Owner 贝克诺顿(浙江)制药有限公司
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