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

Quinazoline derivatives and their preparation and use

A quinazoline and derivative technology, applied in the field of drug synthesis, can solve the problems of increasing the difficulty of curing and the probability of recurrence, and achieve good inhibitory activity and selectivity

Inactive Publication Date: 2016-05-18
SHENYANG POLYTECHNIC UNIV
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

If the receptors of cancer cells are overexpressed or overactivated, the cancer cells will grow in large numbers, thus increasing the difficulty of curing and the probability of recurrence

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
  • Quinazoline derivatives and their preparation and use
  • Quinazoline derivatives and their preparation and use
  • Quinazoline derivatives and their preparation and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] 1-(4-((4-((6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)furan-2-yl)quinazolin-4-yl)amino) Synthesis of phenoxy)methyl)piperidin-1-yl)ethanone (Ⅰ-1)

[0039]

[0040] Add 500 mL of ethanol and 5 mL of sulfuric acid into a 1000 mL four-neck reaction flask, then add 50 g of 1-(4-((4-nitrophenoxy)methyl)piperidin-1-yl)ethanone 1, and heat up to reflux. Add 60g of reduced iron powder several times in small amounts, and continue the reflux reaction for 3 hours after adding the iron powder. Cool to room temperature and add ammonia water dropwise to adjust the pH to about 9, filter, remove iron sludge, and wash with water. The filtrate was adjusted to pH=4 with hydrochloric acid, the product was precipitated, filtered, and the filter cake was dried to obtain 36.8 g of 1-(4-((4-aminophenoxy)methyl)piperidin-1-yl)ethanone 2. 1 HNMR(400MHz,DMSO):δ1.34-1.59(m,4H,CH 2 ),2.00(m,1H,CH),2.36(s,3H,CH 3),3.20-3.40(m,4H,CH 2 ),3.90(d,2H,CH 2 ),6.50-6.80(dd,4H,ArH); ESI-MS: m / z249...

Embodiment 2

[0045] Cyclopropyl 1-(4-((4-((6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)furan-2-yl)quinazolin-4-yl )amino)phenoxy)methyl)piperidin-1-yl)methanone (Ⅰ-2) synthesis

[0046]

[0047] Prepared according to the same method as in Example 1, cyclopropyl (4-((4-nitrophenoxy) methyl) piperidin-1-yl) ketone is reduced by iron powder to obtain compound (4-(( 4-aminophenoxy)methyl)piperidin-1-yl)cyclopropylmethanone, reacted with 4-chloro-6-iodoquinazoline, and then reacted with 5-formyl-2-furylboronic acid, Finally react with 2-methanesulfonylethylamine to obtain the target compound I-2, 1 HNMR(400MHz,DMSO):δ0.72-0.93(m,4H,CH 2 ),1.15-1.17(m,1H,CH),1.34-1.59(m,4H,CH 2 ),2.00(m,1H,CH),2.83(s,3H,CH 3 ),3.11(m,2H,CH 2 ),3.20-3.40(m,4H,CH 2 ),3.53(m,2H,CH 2 ),3.67(s,2H,CH 2 ),3.90(d,2H,CH 2 ),6.39(d,1H,ArH),6.74(d,2H,ArH),7.35(d,1H,ArH),7.60(d,2H,ArH),7.93(d,1H,ArH),8.20(m ,2H,ArH),8.60(s,1H,ArH);ESI-MS:m / z604[M+H] + .

Embodiment 3

[0049] 6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)furan-2-yl)-N-(4-((1-(methylsulfonyl)piperidin-4-yl Synthesis of )methoxy)phenyl)quinazolin-4-amine (Ⅰ-3)

[0050]

[0051] Prepared according to the same method as in Example 1, 1-methylsulfonyl-(4-((4-nitrophenoxy)methyl)piperidine was reduced by iron powder to obtain compound (4-((1-methylsulfonyl) Acyl)piperidin-4-yl)methoxyaniline, then reacted with 4-chloro-6-iodoquinazoline, then with 5-formyl-2-furylboronic acid, and finally with 2-methanesulfonylethylamine The reaction gives the target compound I-3, 1 HNMR(400MHz,DMSO):δ1.34-1.59(m,4H,CH 2 ),2.00(m,1H,CH),2.83(s,3H,CH 3 ),2.96(s,3H,CH 3 ),3.11(m,2H,CH 2 ),3.20-3.40(m,4H,CH 2 ),3.53(m,2H,CH 2 ),3.67(s,2H,CH 2 ),3.90(d,2H,CH 2 ),6.39(d,1H,ArH),6.74(d,2H,ArH),7.35(d,1H,ArH),7.60(d,2H,ArH),7.93(d,1H,ArH),8.20(m ,2H,ArH),8.60(s,1H,ArH);ESI-MS:m / z614[M+H] + .

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 technical field of medicinal chemistry, and relates to quinazoline derivatives of general formula (I) and their preparation methods, and their physiologically acceptable salts formed with inorganic or organic acids or bases, and pharmaceutical compositions containing them , and its application in the preparation of medicines for treating diseases, especially the medicines for diseases characterized by abnormal erbB family PTK activity. Said compounds have valuable pharmacological properties, in particular an inhibitory effect on signal transduction caused by tyrosine kinases.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a preparation method of quinazoline derivatives and their use as pharmaceutical preparations. Background technique [0002] Tyrosine Kinase Inhibitor (TyrosineKinaseInhibitor), mainly acts on epidermal growth factor receptor (EpidermalGrowthFactorReceptor, EGFR). EGFR has an important influence and control correlation on the growth of cancer cells. If the receptors of cancer cells are overexpressed or overactivated, the cancer cells will grow in large numbers, thereby increasing the difficulty of curing and the probability of recurrence. EGFR receptors can be divided into four types of human epidermal growth factor receptors (HumanEpidermalReceptor). The first type is usually called EGFR, the second type is called HER2, and the other types are third and fourth. Among these four types, the presence or absence of type II receptors is the most important, because the overexpression a...

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): C07D405/14A61K31/517A61P35/00
CPCC07D405/14
Inventor 蔡志强李素君侯玲胡志泉孙洪涛李志利郭洪彬蔡奥飞
Owner SHENYANG POLYTECHNIC 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