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

Application of methoxy-substituted phenylamide aminopyrimidine derivative

A phenyl and methyl technology, applied in the application field of methoxy substituted phenyl amide aminopyrimidine derivatives, can solve the problems of EGFR kinase toxicity, drug resistance and the like

Pending Publication Date: 2020-09-04
SHANGHAI INST OF PHARMA IND +1
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to provide a methoxy-substituted phenylamide aminopyrimidine derivative in order to overcome the existing EGFR inhibitors in the prior art that have certain toxicity and drug resistance to wild-type EGFR kinases. Application of things

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
  • Application of methoxy-substituted phenylamide aminopyrimidine derivative
  • Application of methoxy-substituted phenylamide aminopyrimidine derivative
  • Application of methoxy-substituted phenylamide aminopyrimidine derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] Example 1 N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indole-3 Preparation of -yl)-2-pyrimidinyl]amino]phenyl]-2-(3-N,N-dimethylamino)benzamide

[0092]

[0093] The compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidine- 2-yl)benzene-1,2,4-triamine (1.0g, 2.24mmol, 1eq), 3-(N,N-dimethylamino)benzoic acid (445mg, 2.69mmol, 1.2eq) and HATU (1.28 g, 3.37mmol, 1.5eq) was dissolved in dichloromethane (20ml), DIPEA (1.11ml, 6.73mmol, 3.0eq) was added, and after stirring at room temperature for 4 hours, the reaction solution was washed three times with water, dried and concentrated, and the crude product was subjected to column chromatography ( dichloromethane / methanol) to give the product (1.33g).

[0094] 1 H NMR (400MHz, DMSO-d 6 ):δ=10.37(s,1H),9.30(s,1H),8.79(s,1H),8.36(d,J=5.2Hz,1H),8.25(d,J=8.0Hz,1H),7.91 (s,1H),7.53(d,J=8.0Hz,1H),7.36(t,J=8.0Hz,1H),7.29-7.19(m,4H),7.19-7.12(m,1H),7.11( s,1...

Embodiment 2

[0095] Example 2 N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indole-3 Preparation of -yl)-2-pyrimidinyl]amino]phenyl]-2-(2-chloro)benzamide

[0096]

[0097] Reference Example 1 prepares N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-ind Indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-(2-chloro)benzamide (1.31g)

[0098] 1 H NMR (400MHz, DMSO-d 6 ):δ=10.91(s,1H),9.22(s,1H),8.70(s,1H),8.35(d,J=5.2Hz,1H),8.25(d,J=8.0Hz,1H),7.96 (s,1H),7.63(dd,J=7.2,2.4Hz,1H),7.59(dd,J=7.6,1.6Hz,1H),7.55-7.45(m,3H),7.28-7.21(m,2H ),7.19-7.12(m,1H),7.10(s,1H),3.87(s,3H),3.86(s,3H),2.89(s,2H),2.74(s,3H),2.16(s, 2H), 1.76ppm (s, 6H); ES-API (m / z): calculated value C 32 h 34 ClN 7 o 2 [M+H]+, 584.2; theoretical value, 584.2.

Embodiment 3

[0099] Example 3 N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indole-3 -yl)-2-pyrimidinyl]amino]phenyl]-2-(2,6-difluoro)benzamide

[0100]

[0101] With reference to Example 1, N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-ind Indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-(2,6-difluoro)benzamide (1.29 g).

[0102] 1 H NMR (400MHz, DMSO-d 6 ):δ=11.12(s,1H),9.17(s,1H),8.64(1H),8.35(d,J=5.2Hz,1H),8.24(d,J=8.0Hz,1H),7.97(s ,1H),7.65-7.55(m,1H),7.52(d,J=8.0Hz,1H),7.33-7.21(m,4H),7.20-7.12(m,1H),7.10(s,1H), 3.87(s,3H),3.85(s,3H),2.89(t,J=5.6Hz,2H),2.74,(s,3H),2.19(t,J=5.6Hz,2H),1.81ppm(s ,6H); ES-API(m / z): calculated value C 32 h 33 f 2 N 7 o 2 [M+H]+, 586.3; theoretical value, 586.3.

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 application of a methoxy-substituted phenylamide aminopyrimidine derivative. The compound shown in the formula I or pharmaceutically acceptable salt thereof can be used for preparing an EGFR inhibitor. The compound shown in the formula I or the pharmaceutically acceptable salt thereof has an inhibiting effect on EGFR, has low toxicity to normal cells and has high patent medicine prospects.

Description

technical field [0001] The invention relates to the application of a methoxy-substituted phenylamide aminopyrimidine derivative. Background technique [0002] There is a specific cysteine ​​(Cys797) residue near the opening of the ATP-binding domain of the EGFR receptor family, and the cysteine ​​residue at a similar position only exists in EGFR, HER2, HER4, Jak3, Blk, Lkb1, 95Bmx, Among the 11 kinases including Btk, Itk, Tec and Txk. This specific cysteine ​​residue is different from glutamic acid or serine residues of other kinases, which is nucleophilic and can undergo Michael addition reaction with electrophilic Michael acceptor groups. An electrophilic Michael acceptor group is introduced into the inhibitor to allow Michael addition reaction with nucleophilic Cys797 to irreversibly prevent the binding of the kinase to ATP, thereby achieving irreversible selective inhibition of the EGFR kinase and improving the strength of the inhibitor. [0003] The current EGFR inhi...

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): A61K31/506A61K31/555A61P35/00A61P35/02C07D403/04C07D403/14C07F17/02
CPCA61K31/506A61K31/555A61P35/00A61P35/02C07D403/04C07D403/14C07F17/02
Inventor 黄军海王彩月谭绍英吕志良李明胡锦
Owner SHANGHAI INST OF PHARMA IND
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