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

EGFR inhibitor and preparing method and application thereof

An epidermal growth factor and inhibitor technology, applied in the field of medicine, can solve problems such as drug failure and drug resistance in patients, and achieve the effect of solving drug resistance problems

Inactive Publication Date: 2015-10-28
NANJING LEIKEXING BIOTECH CO LTD
View PDF5 Cites 31 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

One of the mutations occurs at the gatekeeper residue 790 of the EGFR tyrosine kinase, and the original L-threonine (T) at this site is replaced by L-methionine (M), which is called T790M Mutation, after the mutation, EGF tyrosine kinase R no longer combines with gefitinib and erlotinib, so that the drug loses its effect and the patient develops drug resistance

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
  • EGFR inhibitor and preparing method and application thereof
  • EGFR inhibitor and preparing method and application thereof
  • EGFR inhibitor and preparing method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: 2-{4-fluoro-2-methoxy-5-[N,N-dimethylaminomethyl-(E)-acrylamido]}anilino-4-(1-methyl- Preparation of 3-indolyl)pyrimidine (compound 101)

[0034]

[0035] Preparation of 3-(2-chloro-4-pyrimidinyl)-1-methylindole

[0036]

[0037] 2,4-Dichloropyrimidine (450g, 3.02mol) was dissolved in ethylene glycol dimethyl ether (6L), stirred in an ice bath, aluminum chloride was added in batches, and then stirred and reacted at room temperature for half an hour. N-methylindole (400 g, 3.05 mol) was added dropwise. Then heated to 80°C and stirred for 4 hours. Liquid chromatography-mass spectrometry (LCMS) detected that the reaction was complete. Stop the reaction, cool down to room temperature, slowly introduce the reaction solution into ice water (18 L), stir rapidly, a large amount of orange-red solid is precipitated, filter with suction, wash the filter cake with cold water three times, and dry the obtained filter cake to obtain a light red solid crude product ...

Embodiment 2

[0053] Example 2: 2-{4-N,N-dimethylamino-2-methoxy-5-[N,N-dimethylaminomethyl-(E)-acrylamido]}anilino- Preparation of 4-(1-methyl-3-indolyl)pyrimidine (compound 102)

[0054]

[0055] Preparation of 2-(4-N,N-Dimethylamino-2-methoxy-5-nitro)anilino-4-(1-methyl-3-indolyl)pyrimidine

[0056]

[0057] 2-(4-Fluoro-2-methoxy-5-nitro)anilino-4-(1-methyl-3-indolyl)pyrimidine (400 mg, 1.012 mmol) was dissolved in N,N-di Dimethylamine (50mg, 1.113mmol) and N,N-diisopropylethylamine (500mg, 4.048mmol) were added to methylformamide (5ml), and the reaction was stirred at 86°C for 3 hours. LCMS detected that the reaction was complete. Cool to room temperature, add the reaction solution dropwise to stirring water, a large amount of solids are precipitated, filter with suction, wash the filter cake with a small amount of water, dissolve the filter cake in dichloromethane, add dropwise to stirring petroleum ether for beating treatment, the obtained solid is pumped Filter dry. Obtaine...

Embodiment 3

[0064] Example 3: 2-{4-(1-methyl-N,N-dimethylaminoethyl)amino-2-methoxy-5-(3'-N,N-dimethylamine Preparation of methyl-acryloyl)-amino}anilino-4-(1-methyl-3-indolyl)pyrimidine (compound 103)

[0065]

[0066] 2-{4-(1-methyl-N,N-dimethylaminoethyl)amino-2-methoxy-5-nitro}anilino-4-(1-methyl-3- Preparation of indolyl)pyrimidine

[0067]

[0068] 2-(4-Fluoro-2-methoxy-5-nitro)anilino-4-(1-methyl-3-indolyl)pyrimidine (Intermediate A) (150 g, 0.381 mol) was dissolved in Dimethylsulfoxide (3L), stirred at room temperature, added N,N,N-trimethylethylenediamine (55g, 0.534mol) and N,N,-diisopropylethylamine (123g, 0.953 mol), then heated to 86°C, and stirred for three hours. LCMS detected that the reaction was complete. Stop the reaction, cool to room temperature, slowly add the reaction solution into stirring ice water (10L), a large amount of orange-red solid precipitates, filter with suction, and dry the filter cake to obtain 170g of solid, purity: 98%, yield: 94% . LC-M...

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 an EGFR inhibitor. The EGFR inhibitor is of the structure shown in the formula (I) and is a compound including alpha, beta-unsaturated carboxylic acid amides. Meanwhile, the invention discloses a preparing method of the compound and the application of the compound serving as a protein tyrosine kinase inhibitor, especially the inhibiting function on T790M variant EGFR as the EGFR inhibitor, and the application on treating diseases such as the kidney cancer, the ling cancer, the prostate cancer, the pancreatic cancer the breast cancer and the spongiocytoma which are related to EGFR over expression. The structure is shown in the specification.

Description

technical field [0001] The invention relates to the field of medicine, in particular to an epidermal growth factor receptor EGFR inhibitor and its preparation method and application. Background technique [0002] Epidermal Growth Factor Receptor EGFR (Epidermal Growth Factor Receptor) is a kind of ErbB receptor family, is a kind of glycoprotein, belongs to tyrosine kinase type receptor, cell membrane runs through, molecular weight 170KDa. EGFR is located on the surface of the cell membrane and binds to ligands to activate EGF and TGF (transforming growth factor). After activation, EGFR is converted from a monomer to a dimer and activates its intracellular kinase pathway to guide downstream phosphorylation, including MPAK, Akt and JNK pathways, and induce cell proliferation. Studies have shown that there are high or abnormal expressions of EGFR in many solid tumors, and EGFR is related to the proliferation, angiogenesis, tumor invasion, metastasis and inhibition of apoptosis...

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): C07D403/04A61K31/506A61P35/00
CPCC07D403/04
Inventor 不公告发明人
Owner NANJING LEIKEXING BIOTECH 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