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

Quinazoline derivatives and preparation method and application thereof

A technology of quinazoline and derivatives, which is applied in the field of quinazoline derivatives and can solve problems such as side reactions

Inactive Publication Date: 2011-08-10
SHANGHAI ALLIST PHARM CO LTD
View PDF2 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The quinazoline EGFR inhibitors reported so far are all ATP competitive inhibitors of wild-type EGFR, which act non-specifically on EGFR T790M, resulting in some side effects

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 preparation method and application thereof
  • Quinazoline derivatives and preparation method and application thereof
  • Quinazoline derivatives and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] N-[4-(3-chloro-4-hydroxy-phenylamino)-7-methoxy-quinazolin-6-yl-]-crotonamide

[0050]

[0051] In a flask equipped with a condensing device, the raw material (Ia-1) 4-hydroxy-3-chloroaniline 1.37 g (5.6 mmol) and (Ib-1) 6-nitro-7-methoxy-4- 1.20g (5.7mmol) of chloro-quinazoline was dissolved in 80ml of isopropanol and reacted under reflux for 3h. A large amount of yellow solid precipitated in the system, filtered, and washed with saturated sodium bicarbonate aqueous solution to pH=8. The sample was dried in vacuum, and the compound was identified as (Ic-1).

[0052] Add 1.60g (3.77mmol) of the above (Ic-1) compound, 1.05g (18.85mmol, 5eq) of reduced iron powder, 2ml of glacial acetic acid, 40ml of methanol, and reflux under an oil bath at 85℃ into a flask equipped with reflux condenser After 2.5 hours of reaction, the iron powder was removed by filtration, the filtrate was diluted with ethyl acetate, washed with sodium bicarbonate solution, washed with water, and the organ...

Embodiment 2

[0058] N-[4-(3-Chloro-4-hydroxy-phenylamino)-quinazolin-6-yl-]-crotonamide

[0059]

[0060] In a flask equipped with a condenser, the raw materials (Ia-1) 4-hydroxy-3-chloroaniline 1.37 g (5.6 mmol) and (Ib-2) 6-nitro-4-chloro-quinazoline 1.20 g (5.7 mmol) was dissolved in 80ml of isopropanol and reacted under reflux for 3h. A large amount of yellow solid precipitated in the system, filtered, and the solid was washed with saturated sodium bicarbonate aqueous solution to pH=8. The sample was dried in vacuum, and the compound was identified as (Ic-2).

[0061] Add 1.60g (3.77mmol) of the above (Ic-2) compound, 1.05g (18.85mmol, 5eq) of reduced iron powder, 2ml of glacial acetic acid, 40ml of methanol, and reflux under an oil bath at 85°C into a flask equipped with a reflux condenser After 2.5 hours of reaction, the iron powder was removed by filtration, the filtrate was diluted with ethyl acetate, washed with sodium bicarbonate solution, washed with water, and the organic phase was...

Embodiment 3

[0067] N-[4-(3-Chloro-4-hydroxy-phenylamino)-quinazolin-6-yl-]-acrylamide

[0068]

[0069] In a 100ml flask, add 1.2g (3.04mmol) of the (Id-2) compound of Example 2 above, 0.8ml (6.1mmol, 2eq) of triethylamine, 1.02ml (12.1mmol, 4eq) of acryloyl chloride under ice bath ), THF40ml, gradually warmed to room temperature for reaction. After 3h, the reaction was stopped, filtered, the solid was washed with water to neutrality, and dried to obtain 1.1g of solid. The compound was identified as (3) with a yield of 68%.

[0070] H 1 -NMR (400MHz, CDCl 3 +DMSO):

[0071] δ8.63(s, 1H), 8.53(s, 1H), 8.14(s, 3H), 7.71-7.64(dd, 2H), 7.23(s, 1H), 7.06-7.02(m, 2H), 6.78- 6.76(d, 1H), 5.92-5.89(d, 1H), 5.54-5.48(m, 1H)

[0072] ESI(+): 341

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 quinazoline derivatives serving as irreversible tyrosine kinase inhibitors, and use of the derivatives as inhibitors for human epidermal growth factor receptor (EGFR) mutant T790M and anticancer agents. The invention also relates to a preparation method for the quinazoline derivatives, and a medicinal composition containing the quinazoline derivatives.

Description

Technical field [0001] The present invention relates to a class of quinazoline derivatives as tyrosine kinase inhibitors, and the application of these derivatives as inhibitors of epidermal growth factor receptor (EGFR) mutant T790M and anticancer agents. The present invention also relates to its preparation method and a pharmaceutical composition containing quinazoline derivatives. Background technique [0002] Cancer is considered a disease of the intracellular signal transduction system or signal transduction mechanism. The most common cause of cancer is a series of defects, which can be defects in protein (when it is mutated), or defects in regulation of the amount of protein in cells, resulting in overproduction or underproduction of protein. Mutations in cell surface receptors (the mutations usually transmit signals to cells through tyrosine kinases) can cause kinases to be activated in the absence of ligands and transmit signals that do not actually exist. Alternatively,...

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): C07D239/94A61K31/517A61P35/00
CPCC07D239/94A61K31/517A61P35/00
Inventor 姜勇郭建辉
Owner SHANGHAI ALLIST PHARM CO LTD
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