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

5-fluorouracil spliced 4-aniline quinazoline compound as well as preparation method and application thereof

A technology of aniline quinazoline and fluorouracil, applied in the field of chemistry, can solve the problems of drug resistance mutation, inability to effectively kill cancer cells, drug resistance and the like

Active Publication Date: 2022-05-06
遵义医药高等专科学校
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these 4-aniline quinazoline compounds only have an inhibitory effect on the growth of cancer cells, but cannot effectively kill cancer cells, and about 60% of patients have drug-resistant mutations at the T790M action site after about 10 months of use. And the choice of follow-up drug treatment is very limited, and almost all other inhibitors of this type have similar drug resistance problems

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
  • 5-fluorouracil spliced 4-aniline quinazoline compound as well as preparation method and application thereof
  • 5-fluorouracil spliced 4-aniline quinazoline compound as well as preparation method and application thereof
  • 5-fluorouracil spliced 4-aniline quinazoline compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] The chemical synthesis of 5-fluorouracil splicing 4-aniline quinazoline compounds (E1) with formula (I), the preparation methods are shown in Table 1, the preparation methods of compounds E2~E3 are exactly the same, but it should be emphasized that the compounds of the present invention are not limited to those shown in Table 1.

[0034] Table 1 has the chemical synthesis of formula (I) 5-fluorouracil splicing 4-aniline quinazoline compounds

[0035]

[0036] Take the 5-fluorouracil alkyl intermediate (A, 6.0g, 23.9mmol) in a 250mL reaction flask, add 50mL of anhydrous tetrahydrofuran and stir to dissolve, then add azidotrimethylsilane (13.5mL, 95.6mmol, 4.0eq. ) and 1mol / L tetrabutylammonium fluoride tetrahydrofuran solution (95.6mL, 95.6mmol, 4.0eq.). Reaction in an oil bath at 65°C, monitored by thin-layer chromatography (TLC), and the reaction was complete in about 20 hours. The reaction solution was diluted with 400 mL of ethyl acetate, then extracted with 300 ...

Embodiment 2

[0041] The chemical synthesis of 5-fluorouracil splicing 4-aniline quinazoline compound (G1) with formula (I), the preparation method is shown in Table 2, and the preparation method of compound G2 is exactly the same, but it should be emphasized that the compound of the present invention is not limited to Table 2 2 represents the content.

[0042] Table 2 has the chemical synthesis of formula (I) 5-fluorouracil splicing 4-aniline quinazoline compounds

[0043]

[0044] Take 4-anilinoquinazoline compound F1 (100mg, 0.34mmol), compound E (78mg, 0.41mmol, 1.2eq.) in a 25mL eggplant-shaped bottle, add N,N-dimethylformamide 10mL, stir to make it Dissolve completely, add DCC (142mg, 0.69mmol, 2.0eq.), DMAP (84mg, 0.69mmol, 2.0eq.), EDCI (198mg, 1.03mmol, 3.0eq.) successively, continue to stir the reaction at room temperature, thin layer chromatography ( TLC) monitoring, the reaction was complete in about 4 days, the reaction solution was diluted with 40mL ethyl acetate, then ext...

Embodiment 3

[0047]The chemical synthesis of 5-fluorouracil splicing 4-aniline quinazoline compound (J) with formula (II) is shown in Table 3 for the preparation method, but it should be emphasized that the compounds of the present invention are not limited to the content shown in Table 3.

[0048] Table 3 has the chemical synthesis of formula (II) 5-fluorouracil splicing 4-aniline quinazoline compounds

[0049]

[0050] Take 4-anilinequinazoline compound H (50mg, 0.11mmol), compound B (23mg, 0.11mmol, 1.0eq.) in a 25mL eggplant-shaped bottle, add 5mL of N,N-dimethylformamide, stir to make it Completely dissolved, under the condition of avoiding light, add sodium ascorbate (21mg, 0.11mmol, 1.0eq.), cuprous iodide (8mg, 0.04mmol, 0.4eq.), N,N-diisopropylethylamine (17mg , 0.13mmol, 1.2eq.), continue to stir the reaction at room temperature, monitor by thin layer chromatography (TLC), the reaction is complete in about 15 hours, the reaction solution is diluted with 40mL ethyl acetate, and...

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 5-fluorouracil spliced 4-aniline quinazoline compound as well as a preparation method and application of the 5-fluorouracil spliced 4-aniline quinazoline compound. The compound contains 5-fluorouracil and 4-aniline quinazoline skeleton structures at the same time, has potential biological activity, provides a compound source for biological activity screening, has important application value for drug screening and pharmaceutical industry, and has good application prospects through in-vitro anti-tumor activity screening. It is found that the compounds have a remarkable inhibition effect on a human non-small cell lung cancer cell line (A549), a human breast cancer cell line (MCF-7), a human cervical cancer cell line (Hela), a human liver cancer cell line (HepG2) and a human lung adenocarcinoma cis-platinum-resistant strain (A549 / DDP), and the anti-tumor effect strength of part of the compounds is 20 times or above that of positive control erlotinib. The inhibition of EGFR enzyme activity shows that the compound can synergistically play an anti-tumor role from a plurality of signal channels, and has the potential to be developed into a new anti-tumor drug.

Description

technical field [0001] The invention relates to the field of chemical technology, in particular to 5-fluorouracil splicing 4-aniline quinazoline compounds and their application in the treatment / prevention of malignant tumor-related drugs. Background technique [0002] 5-Fluorouracil (5-Fluorouracil, 5-FU) and its derivatives are clinically widely used anti-metabolite anti-tumor drugs, which inhibit the proliferation of tumor cells by interfering with the synthesis of nucleic acids. It has a broad anti-tumor spectrum and can be used alone or in combination with other anti-tumor drugs. It has shown good therapeutic effects on various cancers such as head and neck cancer, breast cancer, gastrointestinal cancer, liver cancer, and urinary system cancer. However, the biggest disadvantage of this type of drug is that it can cause severe gastrointestinal reactions and bone marrow suppression and other adverse reactions during application. The shortcomings of lack of selectivity to ...

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 Applications(China)
IPC IPC(8): C07D403/14C07D239/94A61P35/00
CPCC07D403/14C07D239/94A61P35/00
Inventor 梁光平杨俊田芷杨杰王迪
Owner 遵义医药高等专科学校
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