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

A light-sensitive targeted anti-tumor prodrug that responds to nitroreductase to kill tumor cells and its preparation method and application

A technology of reaction and reaction solution, which is applied in antineoplastic drugs, drug combinations, organic chemistry, etc., and can solve problems such as high toxicity and side effects, low treatment efficiency, and short half-life

Active Publication Date: 2020-08-21
ZHEJIANG UNIV OF TECH
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nitrogen mustards are a class of broad-spectrum antineoplastic drugs used in clinical practice. They have a strong ability to kill cancer cells. low) limitations, making it limited in the clinical application of anti-tumor

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 light-sensitive targeted anti-tumor prodrug that responds to nitroreductase to kill tumor cells and its preparation method and application
  • A light-sensitive targeted anti-tumor prodrug that responds to nitroreductase to kill tumor cells and its preparation method and application
  • A light-sensitive targeted anti-tumor prodrug that responds to nitroreductase to kill tumor cells and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Add compound 1 (200 mg) into a round bottom flask containing 20 mL of DMF, dissolve completely, add 1.2 equivalents of potassium carbonate solid, dissolve 1.2 equivalents of 4-bromomethylnitrobenzene in 10 mL of DMF, and slowly drop into the bottle , reaction at room temperature for 2h. After the reaction, add 20mL DCM to the bottle, wash with water (7×50mL), take the organic phase and wash with saturated sodium chloride (2×50mL), dry over anhydrous sodium sulfate, filter, and remove the organic solvent by rotary evaporation to obtain the crude product. Compound 2 was separated by thin-layer chromatography, the developer used was D / M=10:1, and the yield was 60%.

Embodiment 2

[0040] The synthesis of embodiment 2 prodrug (CM-3)

[0041] Compound 2 (100 mg) was put into a round-bottomed flask containing 20 mL of DCM. After it was completely dissolved, 2 equivalents of DMAP and 2 equivalents of DCC were added in sequence. After activation for 10 min, 2 times the equivalent of chlorambucil was dissolved in 10 mL of DCM and Pour into the bottle and react overnight. Add 20mL DCM to the bottle, wash with water (7×50mL), wash with saturated sodium chloride (2×50mL), dry over anhydrous sodium sulfate, filter, and rotary evaporate to remove the organic solvent to obtain a crude product, which is separated by thin-layer chromatography to obtain the product CM-3, the developer used is DCM(D) / MeOH(M)=15:1, and the yield is 88%. H NMR spectrum see figure 1 , see C NMR figure 2 .

[0042] 1 H NMR (500MHz, CDCl 3 )δ8.28(d, J=8.7Hz, 2H), 7.63(d, J=8.7Hz, 2H), 7.46(d, J=8.8Hz, 1H), 7.08(d, J=8.6Hz, 2H) ,6.97(dd,J=8.8,2.5Hz,1H),6.91(d,J=2.5Hz,1H),6.64(d,J=8.7...

Embodiment 3

[0043] The synthesis of embodiment 3 prodrugs (CM-3)

[0044] Compound 2 (100 mg) was put into a round bottom flask containing 20 mL of DCM. After it was completely dissolved, 0.1 equivalent of DMAP and 1 equivalent of DCC were added in sequence. After activation for 10 min, 1 equivalent of chlorambucil was dissolved in 10 mL of DCM and Pour into the bottle and react overnight. Add 20mL DCM to the bottle, wash with water (7×50mL), wash with saturated sodium chloride (2×50mL), dry over anhydrous sodium sulfate, filter, and rotary evaporate to remove the organic solvent to obtain a crude product, which is separated by thin-layer chromatography to obtain the product CM-3, the developer used is DCM(D) / MeOH(M)=15:1, and the yield is 53%.

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 designs and synthesizes a nitroreductase and light stimulation drug and fluorescence dual release system by taking nitroreductase as a target molecule for drug release based on design and application of nitroreductase and light stimulation drug and fluorescence dual release system. A nitroreductase-light stimulated drug and fluorescence double-release system is designed and synthesized by taking nitroreductase as a target molecule released by the drug as well as boric acid ester as a response group. The determination of the fluorescence of the predrug (CM-3) finds that the predrug (CM-3) can well release fluorescence in response to nitroreductase; meanwhile, compared with other light-sensitive drugs, the predrug has relatively good stability and targeting property; and a research for determining the anti-tumor activity of the predrug by virtue of an MMT method finds that the compound (CM-3) has the anti-tumor activity higher than that of chlorambucil, namely that the targeting property of the compound (CM-3) is higher than that of chlorambucil. According to the predrug, an effective research tool is provided for drug release in cell researches.

Description

technical field [0001] The invention relates to the release of light-sensitive targeted anti-tumor drugs, in particular to the design and application of the anti-tumor drug chlorambucil and fluorescent double release system based on pernitroreductase and light stimulation. Background technique [0002] As an "inexhaustible and inexhaustible" external stimulus, light can control the release of active drugs from light-sensitive prodrugs at a specific time and space without depending on changes in the internal physiological environment of the body. One of the most favored stimuli in the field. In recent years, there have been more and more reports on the preparation of photosensitive prodrugs. Among them, the photosensitive group of coumarin has the advantages of easy synthesis, easy modification, easy detection, fast photolysis speed and clear photolysis mechanism, and has been widely recognized. application. Nitrogen mustards are a class of broad-spectrum antineoplastic dru...

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): C07D311/16A61K31/37A61P35/00
CPCC07D311/16
Inventor 朱勍刘跃朱伸顾晓旭董佳黄金涛邢超俊付曼琳
Owner ZHEJIANG UNIV OF TECH
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