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

Pharmacy use of 4-aniline quinazoline derivatives

A compound and anti-tumor drug technology, applied in the application field of 4-aniline quinazoline derivatives in the preparation of anti-tumor drugs

Active Publication Date: 2009-01-21
江苏艾力斯生物医药有限公司
View PDF11 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, EGFR, through the action of its own tyrosine kinase, leads to the excessive amplification of the weak signal, causing the excessive proliferation of cells

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
  • Pharmacy use of 4-aniline quinazoline derivatives
  • Pharmacy use of 4-aniline quinazoline derivatives
  • Pharmacy use of 4-aniline quinazoline derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] N-{4-[3-chloro-4-(3-fluoro-benzyloxy)phenylamino]-quinazolin-6-yl-}-acrylamide (Compound 1)

[0029]

[0030] In a flask equipped with a condensing device, dissolve 1.20 g (5.7 mmol) of raw material 6-nitro-4-chloro-quinazoline and 1.37 g (5.6 mmol) of 4-m-fluorobenzyloxy-3-chloroaniline In 80ml of isopropanol, reflux reaction for 3h, a large number of yellow solids precipitated in the system, filtered, and the solids were washed with saturated aqueous sodium bicarbonate until pH = 8. The sample was vacuum-dried, and the compound was identified as: 4-[3-chloro-4-(3-fluoro-benzyloxy)phenylamino]-6-nitroquinazoline, with a yield of 67%.

[0031]Add 4-[3-chloro-4-(3-fluoro-benzyloxy)phenylamino]-6-nitroquinazoline 1.60g (3.77mmol) in a flask equipped with a reflux condensing device, reduce Iron powder 1.05g (18.85mmol, 5eq), glacial acetic acid 2ml, methanol 40ml, reflux reaction in an oil bath at 85°C for 2.5h, remove iron powder by filtration, dilute the filtrate wit...

Embodiment 2

[0034] N-{4-[3-chloro-4-(3-fluoro-benzyloxy)phenylamino]-7-methoxy-quinazolin-6-yl-}-acrylamide (Compound 2)

[0035]

[0036] 10.0 g of 4-chloro-2-aminobenzoic acid was dissolved in 50 ml of formamide, refluxed for 5 hours, a large amount of solid precipitated, filtered and dried to obtain 11.5 g of 7-chloroquinazolone. Take 10.0g of quinazolon, slowly add it into 40ml of concentrated sulfuric acid and fuming nitric acid (1:1) mixed acid under ice bath, then raise the temperature to 90°C for 3h, the system becomes clear solution, carefully pour it into 300ml of ice water, and a pale yellow solid precipitates , filtered and washed with water, then dissolved in hot glacial acetic acid, 6-nitro-7-chloroquinazolone crystals were precipitated, and 6.50 g of the product was collected. Take 4.00g of the product and 15ml of phosphorus oxychloride to react with reflux for 2h, pour into ice water, filter and dry to obtain 6-nitro-4,7-dichloroquinazoline intermediate; dissolve it in ...

Embodiment 3

[0039] Embodiment 3: In vitro tumor cell inhibition experiment

[0040] Compounds 1 and 2 were formulated into 5 concentration gradients respectively, and 1×10 5 Different tumor cells, such as A431 (human epidermoid squamous cell carcinoma cells, high expression of erbB1 / low expression of erbB2), Calu-3 (human lung cancer cells, low expression of erbB1 / high expression of erbB2), BT-474 (human breast cancer cells, erbB1 low expression / erbB2 high expression), SKBR3 (human breast cancer cells, erbB1 low expression / erbB2 high expression), SKOV3 (human ovarian cancer cells, erbB1 low expression / erbB2 high expression) suspension 100ul inoculated in 96-well culture plate , and then add 10ul of different concentrations of medicinal solutions to reach the final concentration; place in a 37°C humid incubator, take out the culture plate after 72 hours, add MTT to each well, continue to cultivate for 6hrs, and add 100ul of SDS stop solution. Measure the optical density (OD) value of each...

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 provides a general formula I compound, namely, an application of N-(4-(3- chlorine-4-(3-fluorine-benzyloxy) phenyl amidocyanogen]-quinazoline-6-radical-}-acrylamide or N-(4-(3-chlorine-4-(3-fluorine-benzyloxy) phenyl amidocyanogen)-7-methoxy-quinazoline-6- radical-)-acrylamide in preparing an antineoplastic, in particular to the application in preparing the antineoplastic for treating highly expressed epidermal growth factor receptor. The compound general formula I particularly provides an application of the general formula I compound in preparing drugs for treating erb-B2 highly expressed tumors, such as erb-B2 highly expressed lung cancer, ovarian cancers and breast carcinoma, etc.

Description

technical field [0001] The present invention relates to the pharmaceutical use of 4-aniline quinazoline derivatives. Specifically, the present invention relates to the application of 4-aniline quinazoline derivatives in the preparation of antitumor drugs. Background technique [0002] Cancer is considered a disease of intracellular signaling systems or signaling mechanisms. Cells receive many instructions from outside the cell to guide whether the cell proliferates. The purpose of the signal transduction system is to receive these or other signals on the cell surface, import them into the cell, and then transmit these signals to the nucleus, cytoskeleton, and transport and protein synthetic structure. [0003] The most common cause of cancer is a series of defects, which may be defects in certain proteins (when they are mutated), or defects in the regulation of the amount of proteins in cells, so that proteins are over-produced or under-produced. Often, there is a major l...

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): A61K31/517A61P35/00A61P11/00A61P15/00A61P15/14
CPCC07D239/94A61P11/00A61P15/00A61P15/14A61P35/00
Inventor 姜勇郭建辉
Owner 江苏艾力斯生物医药有限公司
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